Harrison_2002_Psychopharmacology.(Berl)_160_56

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-threshold s stimulation reward procedure (electrodes placed in the posterior lateral hypothalamus) was used to assess the effects of DH beta E (0.5-5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25-5 microg/kg), a dopamine D(1) receptor antagonist, eticlopride (2.5-20 microg/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: DH beta E had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 microg/kg) elevated thresholds when administered alone, and reversed the nicotine-induced potentiation of brain stimulation reward even at a dose (2.5 microg/kg) that had no effect on reward thresholds. Eticlopride (10-20 microg/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.