Neuroprotective Effects of Selegiline Agent Methamphetamine-Prompted Mood-Related Behavior Disorder Mediated via 5-HT2 and D2 Receptors

Background: Many previous studies demonstrated that methamphetamine (METH) abuses can cause mood-related behavioral changes. Previous studies indicated neuroprotective effects of Selegiline. Methods: Seventy male Wistar rats were randomly divided into eight groups (10 rats in each group). Group 1 and Group 2 received normal saline and methamphetamine (10 mg/kg) for 21 days, respectively. Groups 3, 4, and 5 were treated simultaneously with methamphetamine and Selegiline with doses of 10, 15, and 20 mg/kg for 21 days. Groups 6 and 7 are methamphetamine-dependent groups which received 15 mg/kg of Selegiline with haloperidol (as D2 receptor antagonist) and trazodone (as 5-HT2 receptor antagonist) for 21 days, respectively. In days 23 and 24, elevated plus maze (EPM) and open-field test (OFT) were conducted to assess motor activity and mood (anxiety and depression) levels. Results: METH as 10 mg/kg causes reduction of rearing number, ambulation distances, time spent in central square and also number of central square entries in OFT. Also METH administration causes decreases of time spent in open arm and number of open arm entries and increases of time spent in closed arm and number of closed arm entries in EPM. In contrast, Selegiline (of 10, 15, and 20 mg/kg) inhibited behavioral effects of methamphetamine in both OFT and EPM. Also administration of haloperidol and trazodone inhibited these behavioral protective effects of Selegiline and caused decrease of OFT behaviors (rearing number, ambulation distances, time spent in central square, and also number of central square entries) and also caused decreases of spend times in open arm, number of open arm entries, and also increased closed arm time spending and number of entries in closed arm in EPM. Conclusions: Current research showed that Selegiline via mediation of D2 and 5-HT2 receptors inhibits METH-induced neurobehavioral changes, mood-related behavior, and motor activity disturbances.