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.
Carey
Robert J
RJ
VA Medical Center, Syracuse, NY 13210, USA. Careyr@cnyrc.org
DePalma
Gail
G
Damianopoulos
Ernest
E
Hopkins
Anthony
A
Shanahan
Arielle
A
Müller
Christian P
CP
Huston
Joseph P
JP
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