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The Journal of Neuroscience, November 1, 1999, 19(21):9579-9586
A Single Exposure to Amphetamine Is Sufficient to Induce Long-Term Behavioral, Neuroendocrine, and Neurochemical Sensitization in Rats
Louk J. M. J. Vanderschuren, E. Donné Schmidt, Taco J. De Vries, Caroline A. P. Van Moorsel, Fred J.H. Tilders, and Anton N. M. Schoffelmeer Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, 1081 BT Amsterdam, The Netherlands
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 [3H]dopamine from nucleus accumbens, caudate putamen, and medial prefrontal cortex slices and of [14C]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.
Key words: amphetamine; locomotor sensitization; dopamine release; acetylcholine release; nucleus accumbens; hypothalamus-pituitary-adrenal axis; caudate putamen; medial prefrontal cortex
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219579-08$05.00/0
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