A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats.
Repeated treatment with psychostimulant drugs causes long-lasting behavioral sensitization and associated neuroadaptations. Although sensitization induced by a single psychostimulant exposure has also been reported, information on the behavioral and neurochemical consequences of a single psychostimulant exposure is sparse. Therefore, to evaluate whether behavioral sensitization evoked by single and repeated psychostimulant pretreatment regimens represent the same neurobiological phenomenon, the time-dependent expression of behavioral, neurochemical, and neuroendocrine sensitization after a single exposure to amphetamine was investigated in rats. A single exposure to amphetamine (5 mg/kg, i.p.) caused context-independent sensitization of the locomotor effects of amphetamine, which intensified over time. Thus, sensitization to amphetamine was marginal at 3 d after treatment and more evident after 1 week, whereas 3 weeks after treatment, profound sensitization, as well as cross-sensitization, to cocaine was observed. Amphetamine pretreatment caused an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens, caudate putamen, and medial prefrontal cortex slices and of [(14)C]acetylcholine from accumbens and caudate slices. The hyperreactivity of dopaminergic nerve terminals appeared to parallel the development of locomotor sensitization, i.e., whereas hyperreactivity of accumbens dopaminergic terminals increased between 3 d and 3 weeks after treatment, the hyperreactivity of medial prefrontal dopaminergic terminals decreased. Pre-exposure to amphetamine also sensitized the hypothalamus-pituitary-adrenal axis response to amphetamine at 1 and 3 weeks, but not at 3 d after treatment. Because these data closely resemble those reported previously for repeated amphetamine pretreatment, it is concluded that a single exposure to amphetamine is sufficient to induce long-term behavioral, neurochemical, and neuroendocrine sensitization in rats.
Vanderschuren
L J
LJ
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, 1081 BT Amsterdam, The Netherlands.
Schmidt
E D
ED
De Vries
T J
TJ
Van Moorsel
C A
CA
Tilders
F J
FJ
Schoffelmeer
A N
AN
D000109:Acetylcholine / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002352:Carrier Proteins / Q000819:agonists / Q000502:physiology; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011699:Putamen / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000502:physiology; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology; D013997:Time Factors
D001552:Benzazepines; D002352:Carrier Proteins; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D011955:Receptors, Drug; C061445:cocaine receptor; C071262:SK&F 82958; D000324:Adrenocorticotropic Hormone; D000661:Amphetamine; D003042:Cocaine; D000109:Acetylcholine; D004298:Dopamine; D003345:Corticosterone