Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress

Pak J Pharm Sci. 2014 Sep;27(5 Spec no):1459-66.

Abstract

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

MeSH terms

  • Adaptation, Psychological
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Disease Models, Animal
  • Haloperidol*
  • Male
  • Motor Activity*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / prevention & control*
  • Parkinson Disease, Secondary / psychology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT2C / drug effects
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Restraint, Physical*
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology
  • Time Factors

Substances

  • Receptor, Serotonin, 5-HT2C
  • Receptor, Serotonin, 5-HT1A
  • Haloperidol