Time courses of behavioral and regional cerebral metabolic responses to different doses of meta-chlorophenylpiperazine in awake rats.
The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15-30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.
Freo
U
U
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
Soncrant
T T
TT
Ricchieri
G L
GL
Wozniak
K M
KM
Larson
D M
DM
Rapoport
S I
SI
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006016:Glycolates / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*
D003837:Deoxy Sugars; D006016:Glycolates; D010879:Piperazines; D011985:Receptors, Serotonin; D003847:Deoxyglucose; C015068:1-(3-chlorophenyl)piperazine