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

Abstract.

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 (mGluR₅) 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 DHβE (0.5–5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25–5 ug/kg), a dopamine D₁ receptor antagonist, eticlopride (2.5–20 µg/kg), a dopamine D₂ receptor antagonist, LY 314582 (1–20 mg/kg), an mGluR_2/3 agonist, and MPEP (1–9 mg/kg), an mGluR₅ antagonist, on the reward potentiating effects of nicotine (0.25 mg/kg). Results: DHβE had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 µg/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 µg/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 D₁ receptors are involved in the nicotine-induced potentiation of brain stimulation reward, while actions at dopamine D₂, mGlu_2/3 and mGlu₅ receptors did not modulate this effect of nicotine.