Individual differences in responsiveness to single and repeated amphetamine administration: behavioral characteristics and neurochemical correlates
Abstract
The administration of amphetamine to rats results in a relatively wide range of individual differences in responsiveness, both in the initial behavioral patterns as well as in the augmentation response to repeated administration. Therefore we examined the possibility that such differences might reflect intrinsic variation in neurochemical mechanisms regulating responsiveness to amphetamine. Animals were administered a transitional dose (1.75 mg/kg) of amphetamine with regard to the induction of locomotion and continuous stereotypy. On the basis of individual response profiles animals could be separated into two markedly different subgroups, one displaying continuous locomotion (S1), characteristic of lower amphetamine doses, and the other exhibiting a multiphasic pattern, including a prolonged focused stereotypy phase (S2), typically associated with higher amphetamine doses. Examination of regional brain monoamine and metabolite levels revealed distinguishing patterns between the subgroups only in the mesolimbic and mesocortical dopamine systems. With repeated amphetamine administration, the two prominent factors of the augmentation, the emergence of stereotypy and the enhancement of locomotion during the last half of the response, were dissociable between the subgroups. The emergence of stereotypy was confined to S1 animals, whereas only the S2 subgroup displayed the progressive increase in locomotion. Differences in the responsiveness of neurochemical systems to amphetamine…
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Higher doses of stimulants induce hyperactivity and addiction in rat models, but these doses exceed those given clinically.
“Higher doses of stimulants induce hyperactivity and addiction in rat models, but these doses exceed those given clinically (Segal and Kuczenski, 1987).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Segal and Kuczenski, 1987
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- Authors
- Segal, D. S., & Kuczenski, R.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1987-09
- Volume
- 242
- Issue
- 3
- Pages
- 917-926
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2224006131
- Cited by
- 177
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2021: 1 · 2019: 4 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 8 · 2012: 3
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institute of Mental Health (MH 70183)
- National Institute on Drug Abuse (DA-01568, DA04157)
- 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 › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- amphetamine, individual differences, stereotypy, locomotion, dopamine, mesolimbic dopamine system, mesocortical dopamine system, monoamine levels, brain metabolites, rats
- MeSH terms
- Amphetamine, Animals, Brain Chemistry, Dopamine, Dose-Response Relationship, Drug, Homovanillic Acid, Male, Motor Activity, Rats, Inbred Strains, Stereotyped Behavior, Rats
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