The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine.

Rationale: Previous studies have shown that blockade of metabotropic glutamate 5 receptors (mGluR5) results in inhibition of nicotine self-administration in experimental animals. However, these studies have not established the behavioural mechanisms which mediate these effects or the extent to which the effects of mGluR5 antagonism on nicotine self-administration reflect a selective attenuation of nicotine reinforcement.

Objectives: To investigate the effects of antagonising mGluR5 receptors on psychopharmacological responses to nicotine measured using conditioned and unconditioned behaviours.

Results: 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) significantly (P < 0.01) reduced nicotine self-administration and attenuated (P < 0.01) the ability of non-contingent nicotine to enhance the reinforcing properties of a weak reinforcer (extinguishing the house light in an operant chamber). It also attenuated (P < 0.05) the much lower levels of responding for this reinforcer measured in control animals treated with saline. MPEP did not attenuate the increase in locomotor activity induced by acute and repeated nicotine in animals habituated on the test day to the test environment. Furthermore, it had no significant effects on responding for a palatable food reward. By contrast, MPEP significantly reduced (P < 0.001) conditioned locomotor stimulation evoked by pairing nicotine with a specific environment.

Conclusion: The results are consistent with the hypothesis that mGluR5 receptors play an important role in mediating the effects of contextual cues in conditioned behavioural responses to nicotine.