Dopamine transporter, but not tyrosine hydroxylase, may be implicated in determining individual differences in behavioral sensitization to amphetamine
Abstract
Repeated administration of psychostimulants, such as amphetamine and cocaine, results in a long-lasting enhancement of behavioral responses elicited by a subsequent challenge injection of these drugs. This phenomenon has been termed behavioral sensitization. A well established model of individual differences based on the locomotor response to a novel environment has been shown to reliably predict the degree of behavioral sensitization to amphetamine. Rats that have high locomotor response in a novel environment (high responders or HR) develop greater behavioral sensitization to psychostimulants when compared to rats that show low locomotor activity in the same novel environment (low Responders or LR). Therefore, this model is ideal to study genetic factors that may underlie behavioral sensitization to psychostimulants. In this study, adult Sprague-Dawley rats were daily injected with amphetamine (1 mg/kg, i.p.) or saline for 9 days. Locomotor activity was recorded every other day. Following a one week-withdrawal a subsequent challenge of a lower dose of amphetamine (0.5 mg/kg, i.p.) was given to all rats (amphetamine pretreated and saline pretreated) and their locomotor activity was recorded. Our results show that HR rats, but not LR rats, develop behavioral sensitization to the locomotor activating effects of amphetamine. Furthermore, only HR rats pretreated with amphetamine exhibited an increase in dopamine transporter mRNA in the ventral tegmental area (VTA) and substantia nigra (SN). Tyrosine hydroxylase mRNA in the VTA and SN was upregulated in both HR and LR rats pretreated with amphetamine when compared to HR and LR rats pretreated with saline. These results demonstrate the existence of individual differences in behavioral sensitization to amphetamine and suggest that dopamine transporter, but not tyrosine hydroxylase, may be a critical factor in the development and expression of behavioral sensitization to the locomotor activating effects of amphetamine.
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In animals, there are genetic differences in the propensity of individual brains to undergo sensitization, and in the functioning of the mesolimbic dopamine system.
“To date, it has been shown in animals that there are genetic differences in the propensity of individual brains to undergo sensitization, and in the functioning of the mesolimbic dopamine system (Dietz, Tapocik, Gaval-Cruz, & Kabbaj, 2005; Phillips, 1997).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Dietz, Tapocik, Gaval-Cruz, & Kabbaj, 2005
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- Authors
- DIETZ, D., TAPOCIK, J., GAVALCRUZ, M., & KABBAJ, M.
- Affiliations
- Florida State University (US)
- Corresponding author
- KABBAJ, M
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2005-10-15
- Volume
- 86
- Issue
- 3
- Pages
- 347-355
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2059471357
- Cited by
- 41
- References
- 46
- Citations by year
- 2024: 2 · 2022: 3 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 3 · 2012: 1
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- behavioral sensitization, amphetamine, dopamine transporter, tyrosine hydroxylase, individual differences, locomotor activity, novel environment, ventral tegmental area, substantia nigra, psychostimulants, gene expression, genetic factors
- MeSH terms
- Amphetamine, Analysis of Variance, Animals, Behavior, Animal, Cell Count, Exploratory Behavior, Individuality, Male, Motor Activity, Statistics as Topic, Substantia Nigra, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, In Situ Hybridization, Ventral Tegmental Area, Dopamine Uptake Inhibitors, Dopamine Plasma Membrane Transport Proteins, Rats
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