Aniracetam and DNQX affect the acquisition of rapid tolerance to ethanol in mice.
Several studies have emphasized the role of learning in the development of rapid tolerance and have shown that glutamate-mediated neurotransmission plays an important role in this phenomenon. Since the AMPA/kainate receptor system is directly involved in plasticity mechanisms, the influence of this receptor system on rapid tolerance induced by ethanol was studied using the rotarod. In the first experiment, mice were pretreated with aniracetam, an agonist of AMPA/kainate receptors, 30 min before ethanol (2.75 g/kg; IP) treatment, and tested on the rotarod. After 24 h, the groups were tested on the rotarod under ethanol treatment. Aniracetam facilitated the acquisition of rapid tolerance to ethanol. In the second experiment, mice received DNQX, a competitive antagonist of the AMPA receptor, 30 min before ethanol treatment (3 g/kg) and submitted to the rotarod. This dose of ethanol produced tolerance per se. Groups were tested under ethanol treatment (1.75 g/kg) after 24 h. DNQX blocked rapid tolerance to ethanol. Using a similar protocol, the third experiment showed that DNQX blocked the aniracetam-induced facilitation of rapid tolerance to ethanol. Our results show that aniracetam facilitates whereas DNQX blocks ethanol tolerance, suggesting that the non-NMDA receptors are involved in this phenomenon.
Rial
Daniel
D
Dept Farmacologia, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, SC, Brazil.
Takahashi
Reinaldo Naoto
RN
Morato
Gina Struffaldi
GS
D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors
D002492:Central Nervous System Depressants; D000431:Ethanol; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D018697:Nootropic Agents; D011760:Pyrrolidinones; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C036466:aniracetam; C056723:FG 9041