GR205171 blocks apomorphine and amphetamine-induced conditioned taste aversions.
The tachykinin NK1 receptor antagonist, GR205171 ([2-methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-(2S-phenyl -piperidin-3S-yl)-amine), is a potent inhibitor of emesis induced by a wide variety of emetogens. This is in contrast to 5-HT3 (5-hydroxytryptamine3) receptor antagonists, such as ondansetron, which have a more restricted antiemetic profile. The present study evaluated the efficacy of GR205171, in comparison with ondansetron to block the acquisition of a conditioned taste aversion induced by either apomorphine (0.25 mg kg(-1) s.c.) or by amphetamine (0.5 mg kg(-1) s.c.) in rats. Pretreatment with GR205171 (0.1-1.0 mg kg(-1) s.c.) and ondansetron (0.001-0.1 mg kg(-1) s.c.) produced a dose-dependent blockade of conditioned taste aversions evoked by apomorphine. In contrast, the acquisition of conditioned taste aversions induced by amphetamine was inhibited by GR205171 (0.3-0.5 mg kg(-1) s.c.), but only attenuated by ondansetron (0.001-0.1 mg kg(-1) s.c.). These results suggest that tachykinin NK1 receptor antagonists may have potential in the treatment of drug-induced conditioned aversive behaviour and nausea.
McAllister
K H
KH
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Pratt
J A
JA
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D003214:Conditioning, Classical; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D013649:Taste / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
D000662:Amphetamines; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013777:Tetrazoles; D017294:Ondansetron; C103207:vofopitant; D001058:Apomorphine