Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine

Incentive learning underlying cocaine-seeking requires mGluR5 receptors located on dopamine D1 receptor-expressing neurons.

Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse in cocaine addiction often occurs following exposure to environmental stimuli previously associated with drug taking. The metabotropic glutamate receptor, mGluR5, is potentially important in this respect; it plays a central role in several forms of striatal synaptic plasti...

Investigations into the role of the metabotropic glutamate receptor, mGluR5, in incentive learning and some behavioural and neurobiological effects of cocaine

Stimulation of mGluR5 in the accumbens shell promotes cocaine seeking by activating PKC gamma.

Recent studies indicate a critical role for metabotropic glutamate receptor 5 (mGluR5) in the reinstatement of cocaine seeking. However, the signal transduction pathways through which mGluR5s regulate cocaine seeking have not been identified. Here, we show that intra-accumbens shell administration of an mGluR5 (9.0 μm MPEP), but not mGluR1 (50.0 μm YM 298198), antagonist before a priming inject...

Cocaine withdrawal impairs metabotropic glutamate receptor-dependent long-term depression in the nucleus accumbens.

Neuroadaptation in the nucleus accumbens (NAc), a central component of the mesolimbic dopamine (DA) system, has been implicated in the development of cocaine-induced psychomotor sensitization and relapse to cocaine seeking. However, little is known about the cellular and synaptic mechanisms underlying such adaptation. Using a mouse model of behavioral sensitization, we show that animals withdra...

Recent Advances in mGluR5 Receptor Ligands as Potential Treatments for Drug Addiction

Almost a decade has elapsed since the first evidence indicating a role for mGluR5 receptors in regulating the self-administration of drugs of abuse was published. In these initial findings by Chiamulera and colleagues, mice lacking functional mGluR5 receptors did not self-administer cocaine and were indifferent to its locomotor stimulant effects. Since then, numerous pharmacological have confir...