SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats

Like mirtazapine, pretreatment with SB 206553 (1.0, 5.0, and 10.0？mg/kg), attenuated meth-seeking. In contrast, the antagonists, SDZ Ser 082 (0.1, 0.3, and 1.0？mg/kg) and SB 242084 (3.0？mg/kg) had no effect on cue reactivity (CR). SB 242084 (3.0？mg/kg) failed to attenuate the effects of 5.0 and 10？mg/kg SB 206553 on CR. Motor function was largely unaltered by the 5-HT2C ligands; however, SB 206553, at the highest dose tested (10.0？mg/kg), attenuated meth-induced rearing behavior.The lack of effect by 5-HT2C antagonists suggests that meth-seeking and meth-evoked motor activity are independent of endogenous 5-HT acting at 5-HT2C receptors. While SB 206553 dramatically impacted meth-evoked behaviors it is unclear whether the observed effects were 5-HT2C receptor mediated. Thus, SB 206553 deserves further attention in the study of psychostimulant abuse disorders.