Time courses of behavioral and regional cerebral metabolic responses to different doses of meta-chlorophenylpiperazine in awake rats

Brain Res. 1990 Mar 19;511(2):209-16. doi: 10.1016/0006-8993(90)90163-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism*
  • Deoxy Sugars / pharmacokinetics*
  • Deoxyglucose / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Glycolates / pharmacology*
  • Male
  • Motor Activity / drug effects*
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*

Substances

  • Deoxy Sugars
  • Glycolates
  • Piperazines
  • Receptors, Serotonin
  • Deoxyglucose
  • 1-(3-chlorophenyl)piperazine