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Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction

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Sharp, B M·2017·Translational Psychiatry

DOI 10.1038/tp.2017.161PMC PMC5611728

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Abstract

The amygdala integrates and processes incoming information pertinent to reward and to emotions such as fear and anxiety that promote survival by warning of potential danger. Basolateral amygdala (BLA) communicates bi-directionally with brain regions affecting cognition, motivation and stress responses including prefrontal cortex, hippocampus, nucleus accumbens and hindbrain regions that trigger norepinephrine-mediated stress responses. Disruption of intrinsic amygdala and BLA regulatory neurocircuits is often caused by dysfunctional neuroplasticity frequently due to molecular alterations in local GABAergic circuits and principal glutamatergic output neurons. Changes in local regulation of BLA excitability underlie behavioral disturbances characteristic of disorders including post-traumatic stress syndrome (PTSD), autism, attention-deficit hyperactivity disorder (ADHD) and stress-induced relapse to drug use. In this Review, we discuss molecular mechanisms and neural circuits that regulate physiological and stress-induced dysfunction of BLA/amygdala and its principal output neurons. We consider effects of stress on motivated behaviors that depend on BLA; these include drug taking and drug seeking, with emphasis on nicotine-dependent behaviors. Throughout, we take a translational approach by integrating decades of addiction research on animal models and human trials. We show that changes in BLA function identified in animal addiction models illuminate human brain imaging and behavioral studies by more precisely delineating BLA mechanisms. In summary, BLA is required to promote responding for natural reward and respond to second-order drug-conditioned cues; reinstate cue-dependent drug seeking; express stress-enhanced reacquisition of nicotine intake; and drive anxiety and fear. Converging evidence indicates that chronic stress causes BLA principal output neurons to become hyperexcitable.

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Figure 1 Schematic representation of neural projections from multiple brain regions to basolateral amygdala (BLA). The primary neurotransmitters are identified. DRN, dorsal raphe nucleus; NTS, nucleus tractus solitarius; SN, substantia nigra; VTA, ventral tegmental area.CC BY-NC-ND · PubMed Central

Figure 2 Schematic representation of GABA, glutamate and dopamine neural inputs to a GABA interneuron (solid blue) regulating a basolateral amygdala (BLA) principal neuron (solid green) and directly to the principal neuron. The pre- and postsynaptic excitatory (+) and inhibitory (−) effects of each neurotransmitter are shown, as are the glutamate and dopamine projections to BLA.CC BY-NC-ND · PubMed Central

Figure 3 Repeated stress during abstinence increased the reacquisition of operant nicotine self-administration (SA). The reacquisition of nicotine SA was measured under a progressive ratio (PR) schedule begun immediately after the final stress on day 7 (30 min sessions of restraint in a plexiglass cylinder on days 1, 3, 5 and 7 of abstinence from nicotine SA) and followed by an FR5 (fixed ratio: 5 operant lever presses required to obtain 1 infusion of nicotine) schedule. (a) The number of nicotine injections and the final ratio completed under a PR schedule during a 23-h session of reacquisition were significantly increased by repeated restraint stress compared with the non-stress group. (b, c) After the PR session, both nicotine injections and active lever presses during 5 days of reacquisition under an FR5 schedule were also significantly increased by stress (repeated measure ANOVA: P<0.05). *P<0.05 versus non-stress groups (t-test). #P<0.05 versus baseline during the final 3 days of acquisition within group; †P<0.05 stress versus non-stress group at same time interval (t-test). n=5 and 7 for non-stress and stress groups, respectively. Reprinted from Yu et al.147 with permission from the publisher.CC BY-NC-ND · PubMed Central

Figure 4 Reversible disconnection of basolateral amygdala (BLA) and nucleus accumbens core (NAcc) blocked the expression of stress-enhanced operant nicotine self-administration (SA) during reacquisition. GABA receptor agonists, baclofen and muscimol (B+M), or vehicle, were microinjected unilaterally into BLA and contralaterally into NAcc 30 min prior to reacquisition sessions on d1 and 2 (indicated by arrows). Active lever presses and nicotine injections are shown in a, b, respectively. *P<0.05 for within-group comparisons of responses during reacquisition versus the final 3d of acquisition (one-way ANOVA with post hoc Bonferroni comparisons); #P< 0.05 for stress/B+M versus stress/vehicle on the same d (t-test). Reprinted from Yu and Sharp148 with permission from the publisher.CC BY-NC-ND · PubMed Central

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Goldfarb, E. V., & Sinha, R. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.08.005 · Cited by 30
Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain
Wang, L., Gunduz, M. A., Semeano, A. T., Yılmaz, E. C., Alanazi, F. A. H., Imir, O. B., Yener, U., Arbelaez, C. A., Usuga, E., & Teng, Y. D. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02628-2 · Cited by 28
“Furthermore, the spinoparabrachial pathway projects to BLA via PBN for sensory functions [106], and most BLA neurons innervate the hippocampus and neocortex to form bidirectional communications involved in emotion-related memory concerning depression [107, 108].”
Background
Structural, functional, and behavioral significance of sex and gonadal hormones in the basolateral amygdala: A review of preclinical literature
Price, M. E., & McCool, B. A. (2021) · Alcohol · doi:10.1016/j.alcohol.2021.08.001 · Cited by 30
“Dopamine has an important role in regulating BLA-mediated behaviors like fear conditioning (Greba et al., 2001; Heath et al., 2015; Prager et al., 2016; Sharp, 2017).”
Background
Chronic stress increases pain sensitivity via activation of the rACC–BLA pathway in rats
Liu, L., Zhang, R., Chen, L., Zhao, H., Cai, J., Wang, J., Guo, D., Cui, Y., & Xing, G. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.12.009 · Cited by 27
“Also, the BLA is highly associated with a variety of brain functions and diseases, such as cognitive and emotional functions (Sharp, 2017), and the hyperexcitability of BLA neurons is involved in the pathogenesis of SIH.”
Background
Choose your path: Divergent basolateral amygdala efferents differentially mediate incentive motivation, flexibility and decision-making
Keefer, S. E., Gyawali, U., & Calu, D. J. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113306 · Cited by 27
“In humans, neuroimaging studies indicate amygdala activation when presented with drug- associated cues (reviewed in Jasinska et al., 2014; Sharp, 2017).”
Brain responses to positive and negative events in individuals with internet gaming disorder during real gaming
Zhang, Z., Wang, S., Du, X., Qi, Y., Wang, L., & Dong, G. (2023) · Journal of Behavioral Addictions · doi:10.1556/2006.2023.00039 · Cited by 25
“…negative events, considering that the amygdala was known to be the important role in negative emotions (Koob & Volkow, 2016; Schaefer et al., 2002; Sharp, 2017) and abnormal FC between the amygdala and prefrontal cortex (e.g., DLPFC and orbital front lobe) in IGD have been found in previous…”
Melanin-concentrating hormone promotes anxiety and intestinal dysfunction via basolateral amygdala in mice
He, X., Li, Y., Zhang, N., Huang, J., Ming, X., Guo, R., Hu, Y., Ji, P., & Guo, F. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.906057 · Cited by 25
“The amygdala, located in the medial temporal lobe of most mammals (Sah et al., 2003), plays an important role in processing information about anxiety-inducing stimuli, and modulates emotional and behavioral responses (Delgado et al., 2006; Sharp, 2017).”
Background
Basolateral amygdala, nicotinic cholinergic receptors, and nicotine: Pharmacological effects and addiction in animal models and humans
Sharp, B. M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13970 · Cited by 25
Self-citation
Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model
Vitor-Vieira, F., Vilela, F. C., & Giusti‐Paiva, A. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113503 · Cited by 26
Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons
Shao, L.-X., Jiang, Q., Liu, X., Gong, D.-M., Yin, Y., Wu, G., Sun, N.-H., Wang, C.-K., Chen, Q., Yu, C., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0402-8 · Cited by 23
Neurogenetics and Epigenetics of Loneliness
Bowirrat, A., Elman, I., Dennen, C. A., Gondré-Lewis, M. C., Cadet, J. L., Khalsa, J., Baron, D., Soni, D., Gold, M. S., McLaughlin, T., et al. (2023) · Psychology Research and Behavior Management · doi:10.2147/prbm.s423802 · Cited by 23
Alterations in GABAA receptor-mediated inhibition triggered by status epilepticus and their role in epileptogenesis and increased anxiety
Aroniadou‐Anderjaska, V., Figueiredo, T. H., Furtado, M. D. A., Pidoplichko, V. I., Lumley, L. A., & Braga, M. F. M. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106633 · Cited by 23
“It is well-known that repeated stress (or one intense stressful experience that can cause PTSD) can result in a hy-perexcitable amygdala and the development of anxiety (Sharp, 2017; Zhang et al., 2018).”
NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
Komleva, Y. K., Potapenko, I., Lopatina, O. L., Gorina, Y. V., Chernykh, A., Хилажева, Е. Д., Salmina, A. B., & Shuvaev, А. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111588 · Cited by 23
“Previously it was shown, that hyperexcitability of the basolateral nucleus of the amygdala is associated with increased anxiety and often occurs in parallel with various neurodevelopmental, neurodegenerative, and neuropsychiatric disorders [52,53].”
Background
Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities
Ayaz, B. D., & Caudle, R. M. (2023) · Neurobiology of Pain · doi:10.1016/j.ynpai.2023.100124 · Cited by 25
“Stress may reflect a part of the mechanism underlying these clinical comorbidities as BLA is a key brain region involved in stress and activity of BLA neurons is modulated by NA-mediated stress responses (Sharp, 2017).”
Background
Glial Activation in the Thalamus Contributes to Vestibulomotor Deficits Following Blast-Induced Neurotrauma
Dickerson, M. R., Bailey, Z. S., Murphy, S. F., Urban, M. J., & VandeVord, P. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00618 · Cited by 23
Data-driven parcellation and graph theory analyses to study adolescent mood and anxiety symptoms
Ely, B., Liu, Q., DeWitt, S. J., Mehra, L. M., Alonso, C., & Gabbay, V. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01321-x · Cited by 19
Stress- and drug-induced neuroimmune signaling as a therapeutic target for comorbid anxiety and substance use disorders
Smiley, C. E., & Wood, S. K. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108212 · Cited by 24
Elevated Level of PKMζ Underlies the Excessive Anxiety in an Autism Model
Gao, X., Zheng, R., Ma, X., Gong, Z., Xia, D., & Zhou, Q. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00291 · Cited by 22
“Reduced inhibitory function/transmission likely leads to hyperactivity in BLA, which has been reported in various psychiatric disease and stress models (Sharp, 2017).”
Background
The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats
Makhijani, V. H., Franklin, J. P., Voorhies, K. J. V., Fortino, B., & Besheer, J. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05659-w · Cited by 22
Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder
Zhou, Q., Sun, T., Wu, F., Li, F., Liu, Y., Li, W., Dai, N., Tan, L., Li, T., & Song, Y. (2020) · Journal of Traditional Chinese Medical Sciences · doi:10.1016/j.jtcms.2020.10.005 · Cited by 22
Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats
Biagioni, A. F., Cellot, G., Pati, E., Lozano, N., Ballesteros, B., Casani, R., Coimbra, N. C., Kostarelos, K., & Ballerini, L. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120749 · Cited by 20
Dose mediates the protracted effects of adolescent THC exposure on reward and stress reactivity in males relevant to perturbation of the basolateral amygdala transcriptome
Ferland, J. N., Ellis, R. J., Rompala, G. R., Landry, J. A., Callens, J. E., Ly, A., Frier, M. D., Uzamere, T. O., & Hurd, Y. L. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01467-0 · Cited by 21
“Dopamine receptors in the BLA mediate incentive learning, stress reactivity, and social recognition [73, 74] and the interaction between dopamine and CRF regulates amygdala function [75].”
Background
Altered amygdala volumes and microstructure in focal epilepsy patients with tonic–clonic seizures, ictal, and post‐convulsive central apnea
Zeicu, C., Legouhy, A., Scott, C. A., Oliveira, J. F. A., Winston, G. P., Duncan, J. S., Vos, S. B., Thom, M., Lhatoo, S. D., Zhang, H. G., et al. (2023) · Epilepsia · doi:10.1111/epi.17804 · Cited by 20
“31,32 The neural processes accompanying the altered volumes may directly influence the amygdala's control on both respiratory action and cardiovascular instability as shown here and elsewhere.”
Background
α7 nicotinic receptor full agonist reverse basolateral amygdala hyperactivity and attenuation of dopaminergic neuron activity in rats exposed to chronic mild stress
Neves, G. A., & Grace, A. A. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.09.009 · Cited by 22
Anxiety in children and youth with autism spectrum disorder and the association with amygdala subnuclei structure
Hennessy, A., Séguin, D., Correa, S., Wang, J., Martínez-Trujillo, J., Nicolson, R., & Duerden, E. G. (2022) · Autism · doi:10.1177/13623613221127512 · Cited by 20
“It has been postulated that chronic stress causes BLA neurons to become hyperexcitable (Sharp, 2017).”
Background
Disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawal
Chen, W., Zhang, Y., Liang, J., Zhang, Z., Zhang, L., Huang, E., Zhang, G., Lü, L., Han, Y., & Shi, J. (2023) · Science Advances · doi:10.1126/sciadv.adi4462 · Cited by 19
“Specifically, BLA is critical for cue-induced drug seeking and drug taking behaviors ( 25 , 34 , 35 ), while CeA mediates long-lasting negative affective states during withdrawal and incubation of drug craving ( 27 , 36 ).”
Background
Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala
Munshi, S., Rosenkranz, J. A., Caccamise, A. J., Wolf, M. E., Corbett, C. M., & Loweth, J. A. (2019) · Addiction Biology · doi:10.1111/adb.12848 · Cited by 19
Physiological and cognitive changes after treatments of cyclophosphamide, methotrexate, and fluorouracil: implications of the gut microbiome and depressive-like behavior
Corley, C. L., McElroy, T., Sridharan, B., Trujillo, M., Simmons, P., Kandel, S., Sykes, D. J., Robeson, M. S., & Allen, A. R. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1212791 · Cited by 17
“…the basolateral amygdala resulted in interrupted excitatory synaptic transmission causing behavior deficiencies and upregulated immune response seen in these studies (Felix-Ortiz and Tye, 2014; Sharp, 2017; Hu et al., 2022) as well as the hippocampus (Carvajal et al., 2016; Gabrieli et al., 2021).”
Background
Potentially addictive behaviours increase during the first six months of the Covid-19 pandemic
Maráz, A., Katzinger, E., & Yi, S. (2021) · Journal of Behavioral Addictions · doi:10.1556/2006.2021.00079 · Cited by 17
Breakdown of utilitarian moral judgement after basolateral amygdala damage
van Honk, J., Terburg, D., Montoya, E. R., Grafman, J. H., Stein, D. J., & Morgan, B. E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119072119 · Cited by 18
“Human lesion, neuroimaging, and intracranial electroencephalography studies have implicated the amygdala, the nucleus accumbens (NAc), and most prominently the ventral medial prefrontal cortex (vmPFC) as key structures in the neural network of moral decision-making (18, 19, 23–26).”
BackgroundInfluential
The basolateral amygdala regulation of complex cognitive behaviours in the five-choice serial reaction time task
Yin, F., Guo, H., Cui, J., Shi, Y., Su, R., Xie, Q., Chang, J.-R., Wang, Y., & Lai, J. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05260-w · Cited by 16
The stressed orbitofrontal cortex.
Sequeira, M. K., & Gourley, S. L. (2021) · Behavioral Neuroscience · doi:10.1037/bne0000456 · Cited by 16
“For example, the basolateral amygdala projects to multiple layers of the prefrontal cortex, including the OFC (Kita and Kitai, 1990) and is itself subject to structural modification and hyper-excitability due to stressor exposure (Sharp, 2017; Vyas et al., 2002).”
Background
Mechanism of Chronic Stress-Induced Glutamatergic Neuronal Damage in the Basolateral Amygdaloid Nucleus
Wang, S., Liu, X., Shi, W., Qian, Q., Zhang, G., Li, Y., Cong, B., & Zuo, M. (2021) · Analytical Cellular Pathology · doi:10.1155/2021/8388527 · Cited by 16
“As a key component of the limbic system, the amygdala plays a crucial role in the onset and progression of stressinduced phobic anxiety and affective disorders [9, 10].”
Background
A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity
Lo, Y., Yi, P.-L., Hsiao, Y., Lee, T.-Y., & Chang, F. (2023) · Communications Biology · doi:10.1038/s42003-023-05090-9 · Cited by 16
Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective
Xu, C.-X., Huang, W., Shi, X., Du, Y., Liang, J., Fang, X., Chen, H.-Y., & Cheng, Y. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04477-x · Cited by 16
Histone Deacetylase 2-Mediated Epigenetic Regulation is Involved in the Early Isoflurane Exposure-Related Increase in Susceptibility to Anxiety-Like Behaviour Evoked by Chronic Variable Stress in Mice
Peng, L., Liu, X., Yang, Y., Guo, Q., & Zhong, T. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03368-0 · Cited by 15
Regional gray matter volume associated with exercise dependence: A voxel‐based morphometry study
Zhang, F., Wang, S., Feng, Y., Qin, K., Li, H., Wu, B., Jia, Z., & Gong, Q. (2021) · Human Brain Mapping · doi:10.1002/hbm.25585 · Cited by 15
“This process may in some way support the idea that stress plays a role in developing addictions (Ruisoto & Contador, 2019) and in addiction relapse (Sharp, 2017; Sinha & Jastreboff, 2013).”
Background
Optogenetically-induced long term depression in the rat orbitofrontal cortex ameliorates stress-induced reversal learning impairment
Adler, S. M., Girotti, M., & Morilak, D. A. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100258 · Cited by 15
GnRH pulse generator frequency is modulated by kisspeptin and GABA ‐glutamate interactions in the posterodorsal medial amygdala in female mice
Lass, G., Li, X. F., Voliotis, M., Wall, E., de Burgh, R., Ivanova, D., McIntyre, C., Lin, X., Colledge, W. H., Lightman, S. L., et al. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13207 · Cited by 15
Sex-dependent effects of early life stress on reinforcement learning and limbic cortico-striatal functional connectivity
Zühlsdorff, K., López‐Cruz, L., Dutcher, E. G., Jones, J. A., Pama, C., Sawiak, S. J., Khan, S. A., Milton, A. L., Robbins, T. W., Bullmore, E. T., et al. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100507 · Cited by 15
“In rodents, fronto-striatal reorganization results from chronic stress, which leads to a shift from goal-directed actions to habitual behaviours (Dias-Ferreira et al., 2009; Sharp, 2017).”
Electroacupuncture alleviates perioperative hypothalamus-pituitary-adrenal axis dysfunction via circRNA-miRNA-mRNA networks
Wang, Y., Hu, W., Han, J., Zheng, J., Jiang, N., Feng, Y., & Tian, Z. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1115569 · Cited by 15
“In addition to the PVN, the central nucleus of the amygdala (CEA) acts as the physiological response center and also plays a major role in stress mainly through changes in GABAergic neurons (Sharp, 2017).”
Background
Neuroprotective actions of norepinephrine in neurological diseases
Ghasemi, M., & Mehranfard, N. (2024) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-024-02999-w · Cited by 16
“…nerve injury and epilepsy, possibly via facilitating GABAergic neurotransmission and/or suppressing glutamatergic signaling in a variety of circuits and synapses [18, 21, 29, 62, 68, 69, 104, 112, 150, 163, 175, 188, 203]. α1-ARs have been shown to modulate GABA neurotransmission in the brain.”
The neural, behavioral, and epidemiological underpinnings of comorbid alcohol use disorder and post-traumatic stress disorder
Carlson, H. N., & Weiner, J. L. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.09.006 · Cited by 16
Effects of combined brief etomidate anesthesia and postnatal stress on amygdala expression of Cl− cotransporters and corticotropin-releasing hormone and alcohol intake in adult rats
Yang, J., Ju, L.-S., Yang, C., Xue, J., Setlow, B., Morey, T. E., Gravenstein, N. L., Seubert, C. N., Vasilopoulos, T., & Martynyuk, A. E. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.08.019 · Cited by 14
Risk for opioid misuse in chronic pain patients is associated with endogenous opioid system dysregulation
Ballester, J., Baker, A. K., Martikainen, I. K., Koppelmans, V., Zubieta, J.-K., & Love, T. (2022) · Translational Psychiatry · doi:10.1038/s41398-021-01775-z · Cited by 13
“We focused on the NAc and amygdala due to their corresponding functionality in pain, negative affect and, more broadly, their prominent roles in addiction [7, 25, 30, 48, 49].”
Background
Basolateral Amygdala Hyperexcitability Is Associated with Precocious Developmental Emergence of Fear-Learning in Fragile X Syndrome
Svalina, M. N., Rio, C. A. C.-D., Kushner, J. K., Levy, A., Baca, S. M., Guthman, E. M., Opendak, M. M., Sullivan, R. M., Restrepo, D., & Huntsman, M. M. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1776-21.2022 · Cited by 13
Early life exposure to high fructose diet induces metabolic dysregulation associated with sex-specific cognitive impairment in adolescent rats
Barrett, C. E., Jiang, M., O'Flaherty, B. G., Dias, B. G., Rainnie, D. G., Young, L. J., & Menigoz, A. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109220 · Cited by 13
Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and Across the Estrous Cycle
Corbett, C. M., Miller, E. N., Wannen, E. E., Rood, B. D., Chandler, D. J., & Loweth, J. A. (2023) · Neuroendocrinology · doi:10.1159/000531351 · Cited by 13
“Importantly, dopaminergic activity in the VTA can in ﬂ uence glutamatergic projections between the BLA and the medial prefrontal cortex [38], which is one of the major sources of glutamatergic input to the BLA [10].”
BackgroundInfluential
The presence of a social stimulus reduces cocaine-seeking in a place preference conditioning paradigm
Sampedro‐Piquero, P., Ávila‐Gámiz, F., Moreno‐Fernández, R. D., Castilla‐Ortega, E., & Santín, L. J. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119874414 · Cited by 15
“…in the hippocampus and the amygdala not only take part in the cocaine CPP acquisition, but also in the retrieval of drugrelated memories (Castilla-Ortega et al., 2017; Gremel and Cunningham, 2008), the reconsolidation (Wells et al., 2011) and the reinstatement (Bossert et al., 2013; Sharp, 2017).”
Background
Molecular taxonomy of the primate amygdala via single-nucleus RNA sequencing analysis
Zhang, L., Cheng, Y., Wu, S., Lu, Y., Xue, Z., Chen, X., Chen, D., Zhang, B., Qiu, Z., & Jiang, H. (2021) · 中国科学通报：英文版 · doi:10.1016/j.scib.2021.01.017 · Cited by 13
Identifying the neurophysiological effects of memory-enhancing amygdala stimulation using interpretable machine learning
Sendi, M. S. E., Inman, C. S., Bijanki, K. R., Blanpain, L. T., Park, J. K., Hamann, S. B., Gross, R. E., Willie, J. T., & Mahmoudi, B. (2021) · Brain stimulation · doi:10.1016/j.brs.2021.09.009 · Cited by 13
High-fructose diet initiated during adolescence does not affect basolateral amygdala excitability or affective-like behavior in Sprague Dawley rats
O’Flaherty, B., Neigh, G. N., & Rainnie, D. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.042 · Cited by 12
“Furthermore the BLA is hyperactive during MDD, which then normalizes with successful pharmacotherapy [18].”
Influential
Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus
Franco‐García, A., Fernández-Gómez, F.-J., Gómez‐Murcia, V., Hidalgo, J. M., Núñez, C., & Milanés, M. V. (2022) · Biomedicines · doi:10.3390/biomedicines10030588 · Cited by 12
“The BLA is involved in the codification of conditioned stimuli’s emotional value, therefore playing a critical role in goal directed behaviours [16,37,54].”
Background
Traumatic Brain Injury and Alcohol Drinking Alter Basolateral Amygdala Endocannabinoids in Female Rats
Stielper, Z. F., Fucich, E. A., Middleton, J. W., Hillard, C. J., Edwards, S., Molina, P. E., & Gilpin, N. W. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7175 · Cited by 12

Authors: Sharp, B. M.
Affiliations: University of Tennessee Health Science Center (US)
Corresponding author: Sharp, B M
ORCID: Sharp, B M
Venue: Translational Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2017-08-08
Volume: 7
Issue: 8
Pages: e1194-e1194
ISSN: 2158-3188 (ISSN-L)
DOI: 10.1038/tp.2017.161
PMC: PMC5611728
OpenAlex: W2743494055
Cited by: 244
References: 160
Citations by year: 2026: 19 · 2025: 26 · 2024: 31 · 2023: 34 · 2022: 33 · 2021: 41 · 2020: 30 · 2019: 19 · 2018: 10 · 2017: 1
FWCI: 2.02
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0 (tdm)
creativecommons.org/licenses/by-nc-nd/4.0 (vor)
Locations: Translational Psychiatry (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: basolateral amygdala, motivated behavior, addiction, nicotine dependence, drug-seeking behavior, drug relapse, chronic stress, principal neurons, GABAergic circuits, anxiety, fear, post-traumatic stress disorder, autism spectrum disorder, attention deficit hyperactivity disorder, cue reactivity
MeSH terms: Animals, Humans, Motivation, Neurons, Stress, Psychological, Behavior, Addictive, Drug-Seeking Behavior, Basolateral Nuclear Complex

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Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction

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