Chronic treatment with curcumin enhances methamphetamine locomotor sensitization and cue-induced reinstatement of methamphetamine self-administration.

Objectives: Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH).

Methods: The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin 15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days.

Results: Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se.

Conclusions: Curcumin enhanced, rather than inhibited the behavioral effects of METH.