Effects of mGlu1 and mGlu5 receptor antagonists on negatively reinforced learning

Behav Pharmacol. 2005 Mar;16(2):113-21. doi: 10.1097/00008877-200503000-00007.

Abstract

Effects on aversive learning of the novel highly selective mGlu5 receptor antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and mGlu1 receptor antagonist (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) were tested, after systemic administration, in the passive avoidance (PA) and fear potentiated startle (FPS) paradigms. Both MTEP at 10 mg/kg and EMQMCM at 5 and 10 mg/kg, given 30 min before training, impaired acquisition of the passive avoidance response (PAR). Co-administration of MTEP and EMQMCM at doses ineffective when administered alone, produced anterograde amnesia when given 30 min before the acquisition phase. Neither EMQMCM (5 mg/kg) nor MTEP (10 mg/kg) impaired retention of the PAR after direct post-training injections. EMQMCM (5 mg/kg), but not MTEP (10 mg/kg) blocked the PAR when given 30 min before testing. Pre-training administration of MTEP at doses of 2.5 and 5 mg/kg inhibited fear conditioning in the FPS when tested 24 h later. In contrast, EMQMCM was ineffective. Our findings suggest diverse involvement of mGlu1 and mGlu5 receptors in negatively reinforced learning.

MeSH terms

  • Amnesia, Anterograde / chemically induced
  • Animals
  • Avoidance Learning / drug effects*
  • Fear
  • Male
  • Memory / drug effects
  • Pyridines / pharmacology*
  • Quinolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / physiology*
  • Reflex, Startle
  • Reinforcement, Psychology
  • Thiazoles / pharmacology*

Substances

  • (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate
  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
  • Pyridines
  • Quinolines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles
  • metabotropic glutamate receptor type 1