Antagonism at metabotropic glutamate 5 receptors inhibits nicotine- and cocaine-taking behaviours and prevents nicotine-triggered relapse to nicotine-seeking

Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats

“…In addition, an even higher dose of MPEP (10 mg/kg) was without effect on locomotor and exploratory behavior (Henry et al, 2002;Tessari et al, 2004). The present finding that LY341495 (3 mg/kg) reduced both nicotine and food intake in a non-specific manner contrasts with a previous observation that LY341495 had no effect on ethanol self-administration at doses as high as 10 mg/kg in rats (Schroeder et al, 2005).…”

“…In addition, MPEP selectively decreased nicotine-but not food-maintained responding in rats (Paterson et al, 2003;Tessari et al, 2004), and the motivation to self-administer nicotine, as assessed with the progressive ratio schedule of reinforcement (Paterson and Markou, 2005). Further, MPEP reduced nicotine-, cue-and schedule-induced reinstatement of nicotine seeking in rats (Bespalov et al, 2005;Tessari et al, 2004). Thus, blockade of mGlu5 receptors decreases the reinforcing effects of nicotine and may lead to decreases in tobacco smoking in humans.…”

“…In addition, MPEP decreased the conditioned rewarding effects of cocaine in mice (McGeehan and Olive, 2003), of morphine in mice (Aoki et al, 2004;Popik and Wrobel, 2002) and rats (Herzig and Schmidt, 2004), of methamphetamine in mice (Miyatake et al, 2005) and of amphetamine in rats (Herzig et al, 2005), as measured by the conditioned place preference procedure. In addition, MPEP selectively decreased nicotine-but not food-maintained responding in rats (Paterson et al, 2003;Tessari et al, 2004), and the motivation to self-administer nicotine, as assessed with the progressive ratio schedule of reinforcement (Paterson and Markou, 2005). Further, MPEP reduced nicotine-, cue-and schedule-induced reinstatement of nicotine seeking in rats (Bespalov et al, 2005;Tessari et al, 2004).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…The EVH1 domain exhibits a high degree of similarity across Homer isoforms and is essential for Homer interactions with a proline-rich sequence (PPSPF) displayed by proteins regulating drug-induced alterations in neuronal morphology, synaptic architecture, and glutamate receptor signaling/intracellular calcium dynamics. Of particular relevance to drug-induced neuroplasticity [e.g., 20,73,74,[78][79][80][81][82][89][90][91][92][93][94][95][96][97][98][99][100][123][124][125][126][127][128][129][130], these proteins include the mGluR1a and mGluR5 subtypes of Group 1 metabotropic glutamate receptors (mGluRs) [34,102,104,107,[131][132][133][134][135][136][137], the NMDA glutamate receptor scaffolding protein Shank [38,132,138,139], the inositol-1,4,5-triphosphate (IP3) receptor, a down-stream mediator of Group1 mGluR signaling [133,[140]…”

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…Moderate doses of MPEP, a metabotropic glutamate receptor type 5 antagonist (Gasparini et al, 1999), have been shown to decrease nicotine self-administration in rats without affecting responding for food (Kenny et al, 2003 andPaterson et al, 2003). MPEP also decreased drug-seeking behavior during nicotine-and cue-induced reinstatement of nicotine self-administration without affecting food-seeking reinstatement Tessari et al, 2004) showing a role for metabotropic glutamate receptor type 5 activation in the rewarding effects of nicotine. Additionally, in an operant drug discrimination task using 0.6 mg/kg nicotine as a discriminative stimulus for food reinforcement, MPEP partially blocked differential lever pressing controlled by nicotine without affecting response rate .…”