D2 and D4 Receptors Involved in Methamphetamine and p-Chloroamphetamine-induced Amnesia in the Step-through Passive Avoidance Test in Mice

Dopamine D2 and D4 receptors play an important role in cognitive functions. Acute administration of both methamphetamine and p-chloroamphetamine induced amnesia in animals but mechanisms of action remained unclear. The aim of this study was to exam both D2 and D4 receptor activation involved in methamphetamine and p-chloroamphetamine induced amnesia. Dopamine D2 and D4 receptor antagonists were challenged proceeding of acute administration of methamphetamine or p-chloroamphetamine in a passive avoidance test, an amnesia murine model. Acute administration of methamphetamine (3 mg/kg, i.p.) before the training trial induced cognition impairment in passive avoidance test. The amnesic effect could be ameliorated by pretreatment of haloperidol (a dopamine D2 receptor antagonist) and L-745,870 (a dopamine D4 antagonist). Methamphetamine also induced locomotor hyperactivity that was improved by pretreatment of haloperdiol but not by L-745,870. p-Chloroamphetamine (5 mg/kg, i.p.) also induced amnesia in passive avoidance test which was significant attenuated by haloperidol, eticlopride (a selective D2 antagonist) and L-745,870 when these antagonists were administrated 50 min before the training trial or immediately after the training trial. We proposed that both D2 and D4 receptors activation were participated in impairment of memory acquisition induced by methamphetamine and p-chloroamphetamine while dopamine D2 receptors activation was also involved in locomotor hyperactivity induced by methamphetamine.