Dopaminergic and serotonergic autoreceptor stimulation effects are equivalent and additive in the suppression of spontaneous and cocaine induced locomotor activity.
We used the D(2) receptor agonist, apomorphine (APO) and the 5-HT(1A) receptor agonist, 8-OHDPAT (8OH) in a low dose range to stimulate autoreceptors and in this way assess the separate and combined effects of reduced DA and 5-HT activity upon spontaneous and cocaine induced locomotor behavior. Two separate experiments were conducted. In the first experiment, separate groups of rats (N=10) were tested with either saline, 8OH, APO or 8OH plus APO (0.01, 0.025, 0.05 mg/kg). At 0.05 mg/kg, 8OH and APO induced similar dose related decreases (up to approximately 50%) in locomotor activity. The combined 8OH plus APO treatment induced dose-related decreases in locomotion (approximately 90%). At the 0.05 mg/kg dose level, the drug treatments given separately blocked cocaine induced increases in activity and the 8OH and APO inhibitory effects were again additive. In the second experiment, separate groups (N=10) received saline, 0.05 mg/kg APO, 0.05 mg/kg 8OH or 0.05 mg/kg APO plus 0.05 mg/kg 8OH. As in the first experiment, the 8OH and APO given separately reduced locomotor activity by approximately 50% and when given together, locomotor activity was virtually eliminated (reduced 80-90%). When the combined APO/8OH group also received the 5-HT(1A) antagonist, WAY 100635 (0.05 mg/kg), the effect on activity was equivalent to 0.05 mg/kg APO alone. Ex vivo neurochemical measurement of dopamine (DA) and serotonin (5-HT) metabolism confirmed that the APO decreased DA turnover, 8OH decreased 5-HT turnover and the combined treatment reduced both the DA and 5-HT turnover. Thus, for both spontaneous and cocaine induced locomotor behavior, the low dose 8OH and APO treatments suppressed locomotor activity and these effects were additive. These findings indicate that DA and 5-HT systems contribute separately to motoric activation. These results suggest that it is important to consider both DA and 5-HT contributions to disorders of motoric impoverishment such as Parkinson's disease as well as to hyperkinetic states such as those induced by stimulant drugs.
VA Medical Center, Syracuse, NY 13210, USA. Careyr@cnyrc.org
Robert J
RJ
Carey
Gail
G
DePalma
Ernest
E
Damianopoulos
Anthony
A
Hopkins
Arielle
A
Shanahan
Christian P
CP
Müller
Joseph P
JP
Huston
D000818:Animals; D017660:Autoreceptors / Q000819:agonists / Q000378:metabolism*; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017660:Autoreceptors; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D003042:Cocaine