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PubMed · 11411804

Methylphenidate sensitization is modulated by valproate.

K Eckermann·A Beasley·P Yang·O Gaytan·A Swann·N Dafny
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Abstract

Repeated administration of the stimulant methylphenidate (MPD) produces sensitization to its own effects. Glutamate, dopamine, and GABA have been implicated in the underlying mechanism of sensitization to stimulants such as amphetamine and cocaine. We have investigated effects of the GABAergic agent sodium valproate (VAL) on the locomotor response to MPD. Activities of male Sprague-Dawley rats were continuously recorded by a computerized activity monitoring system for 15 days. We studied the dose effect of valproate 1) at 50, 100, and 200 mg/kg (i.p.) on motor activities, 2) on the acute response of motor activities to 2.5 mg/kg MPD, and 3) on behavioral sensitization to subsequent repeated injections of MPD. Valproate alone did not significantly affect motor activities. All three doses of valproate attenuated the acute locomotor effects of MPD, while only the 50 mg/kg dose blocked the development of sensitization to subsequent administration. Possible mechanisms involving substrates for the effect of GABA agonists on sensitization are discussed.

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AnimalsCentral Nervous System StimulantsDrug Administration ScheduleGABA AgentsMaleMethylphenidateMotor ActivityRatsRats, Sprague-DawleyStereotyped BehaviorTime FactorsValproic AcidJournal ArticleResearch Support, Non-U.S. Gov't

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K Eckermann, A Beasley, P Yang, O Gaytan, A Swann, N Dafny. 2001-05-25. Methylphenidate sensitization is modulated by valproate.. https://doi.org/10.1016/s0024-3205(01)01095-5

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