DISCRIMINATIVE STIMULUS PROPERTIES OF ELTOPRAZINE

Rats were trained to discriminate eltoprazine (1-(2,3-dihydro-1,4-benz odioxin-5-yl)piperazine) (1.0 mg/kg p.o.) from demineralized water in a two lever operant procedure. Eltoprazine generalized to the 5-HT1B r eceptor agonist anpirtoline (6-chloro-2-[piperidyl-4-thiol]-pyridine h ydrochloride), the 5-HT1A,1B receptor agonists batoprazine (8-(1-piper azinyl)-2H-1-benzopyran-2-one) and 1-NP (1-(1-naphthyl)piperazine hydr ochloride), and to the 5-HT1B/2C receptor agonist mCPP (1-(3-chlorophe nyl)piperazine dihydrochloride). The 5-HT1A receptor agonist flesinoxa n xin-5-yl)-1-piperazinyl]ethyl]-4-fluorobenzoamide) generalized parti ally and the 5-HT1A receptor antagonist WAY-100635 ethoxyphenyl)-1-pip erazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochlorid e) failed to antagonize the eltoprazine cue, suggesting that 5-HT1A re ceptors are of limited importance in the discriminative stimulus prope rties of eltoprazine. Methiothepin, mCPP, mianserin and alprazolam did not antagonize the eltoprazine cue. The 5-HT1A,1B,1D receptor agonist GR46611X yl)-1H-indol-6-yl]-N-(4-methoxy-benzyl)acrylamide) and the 5 -HT1B,1D receptor antagonist GR127935T (N-[4-methoxy-3-(4-methyl-1-pip erazinyl) phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl) [1,1,- biphenyl]-4-carboxamide) did neither generalize to nor antagonize the eltoprazine cue, whereas (-)-alprenolol showed partial antagonism and substitution. These results show that the eltoprazine discriminative s timulus is mediated by the 5-HT1B receptor, although the lack of good 5-HT1B receptor antagonists weakens this conclusion.