Neonatal hippocampal lesions induced hyperresponsiveness to amphetamine: behavioral and in vivo microdialysis studies
Abstract
The effect of neonatal hippocampal lesions on behavioral sensitivity to amphetamine (AMPH) and dopamine (DA) release in the nucleus accumbens (NAc) were examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on postnatal day 7 (PD7). Spontaneous exploration and AMPH-stimulated locomotor activity were examined on postnatal day 35 (PD35) and day 56 (PD56). Extracellular DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were sampled using in vivo microdialysis while simultaneously AMPH-stimulated locomotion was examined in freely moving rats on PD56. Spontaneous exploration increased in rats with hippocampal lesions relative to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1.5, and 3 mg/kg) enhanced locomotion dose-dependently in both control and lesioned groups. Locomotor activity was higher in lesioned rats than controls following AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on PD56. The basal level of DA in the NAc was not different between the hippocampal and control groups. AMPH (1.5 mg/kg) induced hyperlocomotion in lesioned rats relative to controls. DA release in the NAc for both groups was enhanced following injections of AMPH. However, neonatal hippocampal lesions had no further enhancement on AMPH-stimulated release of DA as compared to the control group. The levels of DOPAC and HVA in the NAc were altered by AMPH but not lesions. The level of 5-HIAA was not influenced by either lesions or AMPH. The results of neonatal lesion-induced hyperlocomotion suggest that an emergence of behavioral hyperresponsiveness to AMPH was dependent on an interaction of lesions, age of examination, and dose of the drug. A dissociation between the effect of AMPH on lesion-enhanced hyperlocomotion and a lack of a lesion-enhanced DA release in the NAc suggest that presynaptic release of DA had no major contribution to lesion-enhanced DA transmission in the mesolimbic DA system.
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Adult rats with a NVHL show hyperlocomotion, increased response to novelty, abnormal social behaviors, exaggerated responses to stress, stimulants and NMDA antagonists, and increased liability for addictive behaviors.
“Behaviorally, adult rats with a NVHL show hyperlocomotion, 39,40 increased response to novelty, 41 abnormal social behaviors, 41 exaggerated responses to stress, stimulants and NMDA antagonists, 39,42 and increased liability for addictive behaviors.43,44”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [40]
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- Authors
- Wan, R.-Q., Giovanni, A., Kafka, S. H., & Corbett, R.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 78
- Issue
- 2
- Pages
- 211-223
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2040181871
- Cited by
- 100
- References
- 56
- Citations by year
- 2021: 1 · 2020: 3 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 4 · 2012: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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
- dopamine release, nucleus accumbens, ventral hippocampus, ibotenic acid, locomotor activity, spontaneous exploration, DOPAC, homovanillic acid, 5-hydroxyindoleacetic acid, mesolimbic dopamine system, rats
- MeSH terms
- Aging, Central Nervous System Stimulants, Animals, Animals, Newborn, Behavior, Animal, Brain Chemistry, Dextroamphetamine, Dopamine, Environment, Exploratory Behavior, Female, Hippocampus, Motor Activity, Nucleus Accumbens, Pregnancy, Dopamine Agents, Rats, Sprague-Dawley, Microdialysis, Rats
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