Nicotine potentiation of brain stimulation reward reversed by DHβE and SCH 23390, but not by eticlopride, LY 314582 or MPEP in rats

Rationale: Systemic nicotine administration increases dopamine and glutamate levels in reward-related brain areas. Nicotine-induced increases of dopamine in the nucleus accumbens are in part mediated by glutamatergic projections to the ventral tegmental area dopamine neurons. Objectives: To assess the effects of actions at acetylcholine, dopamine, presynaptic (mGluR(2/3)) and postsynaptic (mGluR(5)) metabotropic glutamate receptors (mGluRs) on the potentiation of brain stimulation reward induced by systemically administered nicotine (0.125-0.5 mg/kg; free base) in rats. Methods: A discrete-trial current-thresholds stimulation reward procedure (electrodes placed in the posterior lateral hypothalamus) was used to assess the effects of DHPE (0.5-5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25-5 ug/kg), a dopamine D-2 receptor antagonist, eticlopride (2.5-20 mug/kg), a dopamine D-2 receptor antagonist, LY 314582 (1-20 mg/kg), an mGluR(2/3) agonist, and MPEP (1-9 mg/kg), an mGluR(5) antagonist, on the reward potentiating effects of nicotine (0.25 mg/kg). Results: DHPE had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 mug/kg) elevated thresholds when administered alone, and reversed the nicotine-induced potentiation of brain stimulation reward even at a dose (2.5 ug/kg) that had no effect on reward thresholds. Eticlopride (10-20 mug/kg), LY 314582 (10-20 mg/kg) and MPEP (9 mg/kg) elevated thresholds when administered alone but had no effect on the nicotine-induced potentiation of brain stimulation reward. Conclusions: These results indicate that nicotinic and dopamine D-1 receptors are involved in the nicotine-induced potentiation of brain stimulation reward, while actions at dopamine D-2, mGlu(2/3) and mGlu(5) receptors did not modulate this effect of nicotine.