The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior

• Published in: Psychopharmacologia 2004-12, Vol.177 (1-2), p.46-54
• Main Authors: CAREY, Robert J, DEPALMA, Gail, DAMIANOPOULOS, Ernest, MÜLLER, Christian P, HUSTON, Joseph P
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Addictive behaviors; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Cocaine - pharmacology; Dose-Response Relationship, Drug; Drug addiction; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A - physiology; Serotonin 5-HT1 Receptor Agonists
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-004-1917-4

The contribution of the 5-HT(1A) somato-dendritic autoreceptor populations to spontaneous and cocaine-induced locomotion is unclear. To use a low dose range of +/-8-hydroxy-2-(di- n-propylamino)tetralin (8-OHDPAT) to preferentially stimulate 5-HT(1A) autoreceptors and a medium 8-OHDPAT dose range to stimulate both 5-HT(1A) autoreceptors and postsynaptic receptors as pretreatments prior to either saline or cocaine. In experiment 1, either a medium dose of 8-OHDPAT (0.4 mg/kg) or a low dose (0.05 mg/kg) was given as pretreatments 20 min before five separate 20-min open-field tests. In experiment 2, the pretreatments were changed to a low dose range of 8-OHDPAT (0.01-0.05 mg/kg), with or without WAY 100635 (0.01-0.05 mg/kg). In experiment 3, the 8-OHDPAT pretreatments (0.01, 0.025 or 0.05 mg/kg) were administered 20 min prior to saline or cocaine (10 mg/kg) tests. In experiment 4, a medium dose range (0.2-0.3 mg/kg) was given 20 min prior to saline or cocaine (10 mg/kg) tests. Experiment 1 showed that 8-OHDPAT (0.4 mg/kg) tended to increase locomotor activity but that pretreatment with 0.05 mg/kg severely suppressed locomotor activity. In experiment 2, 8-OHDPAT in the low dose range inhibited locomotor activity and this effect was reversed by co-administration of WAY 100635. Experiment 3 showed that the low-dose 8-OHDPAT pretreatment reduced locomotor activity in saline but not cocaine tests. In experiment 4, 8-OHDPAT in the medium dose range enhanced locomotor activity in cocaine tests. It is suggested that the facilitatory effect of 8-OHDPAT on cocaine-induced locomotor stimulation is mediated by inhibition of 5-HT(1A) somato-dendritic autoreceptors.