The role of group I mGlu receptors in the expression of ethanol-induced conditioned place preference and ethanol withdrawal seizures in rats

• Published in: European journal of pharmacology 2011-11, Vol.670 (1), p.154-161
• Main Authors: Kotlinska, Jolanta H., Bochenski, Marcin, Danysz, Wojciech
• Format: Article
• Language: English
• Subjects: Addiction; alcohol abuse; Animal models; Animals; Antagonists; Auditory stimuli; Biological and medical sciences; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Drug addiction; EMQMCM; Epilepsy; Epilepsy, Reflex - complications; Epilepsy, Reflex - metabolism; Epilepsy, Reflex - physiopathology; Ethanol; Ethanol - adverse effects; Expression of CPP; Glutamic acid; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Glutamic acid receptors (metabotropic); Group I mGlu receptors antagonist; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; MTEP; N-Methyl-D-aspartic acid receptors; Nervous system (semeiology, syndromes); Neurology; pharmacology; Pharmacology. Drug treatments; Place preferences; Pyridines - pharmacology; Quinolines - pharmacology; Rats; Rats, Wistar; Receptor, Metabotropic Glutamate 5; receptors; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Reproducibility of Results; Seizures; Seizures - complications; Seizures - metabolism; Seizures - physiopathology; Sound; Spatial Behavior - drug effects; Spatial Behavior - physiology; Substance Withdrawal Syndrome - complications; Thiazoles - pharmacology; Withdrawal; Withdrawal seizure
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.09.025

In animal models, N-methyl-d-aspartate (NMDA) receptors antagonists inhibit physical dependence and the reinforcing effects of ethanol. The group I metabotropic glutamate (mGlu) receptors antagonists (mGlu1 and mGlu5) attenuate excitatory effect of glutamate by functional modulation of the glutamate/NMDA receptors. The objective of the present study was to evaluate the effects of a selective mGlu5 receptors antagonist—MTEP, and mGlu1 receptors antagonist—EMQMCM, on two processes relevant to alcohol addiction: the expression of ethanol-induced conditioned place preference (CPP) paradigm, and ethanol withdrawal audiogenic seizures in rats. Our experiments indicated that EMQMCM at the doses of 5 and 10mg/kg, and MTEP at the doses of 2.5 and 5mg/kg, significantly attenuated the expression of ethanol CPP. Furthermore, both group I mGlu receptor antagonists, i.e. EMQMCM at the dose of 10mg/kg and MTEP at the dose of 5mg/kg, attenuated audiogenic seizures induced by the sound stimulus 12h after withdrawal of ethanol in dependent rats. Our study shows the importance of mGlu5 and mGlu1 receptors for the expression of ethanol-induced CPP and withdrawal seizures, although mGlu5 receptors antagonist (MTEP) was more potent than the antagonist of mGlu1 receptors (EMQMCM).