This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sánchez, H. Articles by Velázquez-Martínez, D. N. Search for Related Content PubMed PubMed Citation Articles by Sánchez, H. Articles by Velázquez-Martínez, D. N. Social Bookmarking                         What's this?

Discriminative stimulus properties of indorenate, a 5-HT1A, 5-HT1B and 5-HT2C agonist: a study in rats

Departamento de Psicofisiología, Facultad de Psicología, Universidad Nacional Autónoma de México, Mexico

D. N. Velázquez-Martínez

Departamento Psicofisiolgía, Facultad de Psicología, Universidad Nacional Autónoma de México, México DF 04510, México; velazque{at}servidor.unam.mx

Indorenate (INDO), initially described as an antihypertensive agent, also has some effects on behaviour, with anxiolytic and anorectic actions being reported. The aim of the present experiment was to examine the activity of INDO at the behavioural level at various serotonin (5-hydroxytryptamine, 5-HT) receptor sites by comparing its stimulus properties with those of other 5-HT receptor agonists and by examining its interactions with some 5-HT antagonists. Rats were trained to discriminate between 10.0 mg/kg INDO (administered intraperitoneally (90 min before the start of the session) from saline. A Fixed Ratio 10 (FR10) schedule of reinforcement was in effect in each drug condition. During generalization test sessions, the discrimination index (DI, responses to drug lever/responses to drug + saline lever) was calculated from the responses emitted before the first reinforcer of the session. DI was a function of the dose of INDO employed. Generalization to the discriminative stimulus properties of INDO was observed with the 5-HT_1A receptor agonist 8-OH-DPAT (1.0 mg/kg produced 90% generalization) and the 5-HT_1B/2C receptor agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) (3.0 mg/kg produced up to 75% generalization). Yohimbine (5.6 mg/kg), buspirone (1.0 mg/kg), 6-chloro-2-(1-piperaziny)pyrazine (1.0 mg/kg) and m-chlorophenyl piperazine (mCPP) (1.0 mg/kg) induced a DI of 70%, 50% and 48% and 55%, respectively. In generalization tests, ritanserin (0.01–1.0 mg/kg) induced saline-like responding. NAN-190 (3.0 mg/kg), a 5-HT_1A receptor antagonist, was able to reduce the DI of INDO to 50%. Although the 5-HT_2C/2A receptor antagonists cinanserin (10.0 mg/kg) and metergoline (0.3 mg/kg) were able to reduce the stimulus properties of INDO to 60% and 30%, respectively, only ritanserin (1.0 mg/kg) reduced the stimulus properties of INDO to 25% with a clear dose–response relationship. The results suggest that INDO acts as an agonist at 5-HT_1A receptor sites, but its activity at 5-HT_1B/2C receptor sites also contributes to its discriminative function.

Key Words: buspirone • drug discrimination • indorenate • mCPP • MK212 • 8-OH-DPAT • TFMPP • yohimbine

Journal of Psychopharmacology, Vol. 15, No. 1, 29-36 (2001)
DOI: 10.1177/026988110101500106


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?