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Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...

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Risperidone treatment increases CB1 receptor binding in rat brain.

Anna Secher1, Henriette Husum, Birgitte Holst

  • 1Laboratory of Neuropsychiatry, Rigshospitalet, Copenhagen, Denmark. anna.secher@rh.regionh.dk

Neuroendocrinology
|October 10, 2009
PubMed
Summary

Antipsychotic risperidone increases cannabinoid receptor 1 (CB(1)) binding in rat brain regions regulating appetite and metabolism. This may explain risperidone-induced weight gain and metabolic dysfunction observed in patients.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Metabolic Research

Background:

  • Antipsychotic medications, like risperidone, frequently cause significant body weight gain.
  • The precise biological mechanisms driving this common side effect remain largely unknown.
  • Potential contributing factors include alterations in appetite and metabolic regulatory pathways.

Purpose of the Study:

  • To investigate the effects of chronic risperidone treatment on key neurochemical factors involved in weight regulation.
  • To examine changes in cannabinoid receptor 1 (CB(1)) expression and related signaling molecules in the rat brain.

Main Methods:

  • Male Sprague-Dawley rats received daily risperidone (1.0 mg/kg) or vehicle for 28 days.
  • Evaluated expression of CB(1) receptors, adiponectin, and other factors in brain tissue.
  • Measured plasma prolactin and ghrelin levels.

Main Results:

  • Risperidone treatment did not alter overall body weight gain but correlated with increased visceral fat mass.
  • Significantly increased CB(1) receptor binding in the arcuate nucleus, hippocampus, and amygdala.
  • Elevated adiponectin mRNA levels were observed following risperidone administration.

Conclusions:

  • Chronic risperidone exposure alters CB(1) receptor binding density in specific brain regions.
  • Increased CB(1) receptor expression in appetite and metabolic control centers may underlie risperidone-induced adiposity.
  • Findings suggest a potential neurobiological mechanism for antipsychotic-related metabolic side effects.