The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior.
BACKGROUND
The contribution of the 5-HT(1A) somato-dendritic autoreceptor populations to spontaneous and cocaine-induced locomotion is unclear.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Carey
Robert J
RJ
VA Medical Center and Upstate Medical University Syracuse, Research & Development (151) 800 Irving Avenue, Syracuse, NY 13210, USA. careyr@cnyrc.org
Depalma
Gail
G
Damianopoulos
Ernest
E
Müller
Christian P
CP
Huston
Joseph P
JP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists
D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine