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). The subjects were male, adult Sprague–Dawley rats. In Experiment 1, the effects of 2 and 4mg/kg curcumin (i.p.) on response rates and breakpoints of .6mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 1days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 2 or 4mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 2, or 4mg/kg curcumin15min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (2mg/kg or 4mg/kg) for 13days 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, 2, or 4mg/kg curcumin. The test was repeated for 14days. Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 4mg/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 (2mg/kg) but not higher (4mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se. Curcumin enhanced, rather than inhibited the behavioral effects of METH. First attempt to study the effect of curcumin on the behavioral effects of METH. Daily treatment of curcumin during abstinence enhanced cue-induced METH seeking. Curcumin had little effect on METH self-administration under FR1 and PR schedules. Chronic administration of curcumin augmented METH-induced locomotor sensitization.
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