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Sex differences in neurochemical effects of dopaminergic drugs in rat striatum.

Publication ,  Journal Article
Walker, QD; Ray, R; Kuhn, CM
Published in: Neuropsychopharmacology
June 2006

Previous data indicate that dopamine neurotransmission is differently regulated in male and female rats. The purpose of the present study was to investigate the dopamine transporter and autoreceptor as potential loci responsible for this sex difference. Fast cyclic voltammetry at carbon-fiber microelectrodes was used to monitor changes in electrically evoked levels of extracellular dopamine in the striata of anesthetized male and female rats before and after administration of an uptake inhibitor, a dopamine D2 antagonist, or a D3/D2 agonist. Administration of 40 mg/kg cocaine ip increased electrically-evoked extracellular dopamine concentrations in both sexes, but to a significantly greater extent in female striatum at the higher stimulation frequencies. The typical antipsychotic, haloperidol, increased dopamine efflux in both sexes but the effect was twice as large in the female striatum. The D3/D2 agonist quinpirole induced an unexpected, transient increase in dopamine efflux following high-frequency stimulation only in females, and evoked dopamine was higher in females across this entire time course. More detailed analysis of cocaine effects revealed no fundamental sex differences in the interaction of cocaine with DAT in vivo or in synaptosomes. These results indicate that nigrostriatal dopamine neurotransmission in the female rat is more tightly regulated by autoreceptor and transporter mechanisms, perhaps related by greater autoreceptor control of DAT activity. Thus, baseline sex differences in striatal dopamine regulation induce different pharmacologic responses. These results contribute to understanding sex differences in stimulant-induced locomotor activity in rats and may have broader implications for neurologic disorders and their pharmacotherapies in humans.

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Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

June 2006

Volume

31

Issue

6

Start / End Page

1193 / 1202

Location

England

Related Subject Headings

  • Time Factors
  • Synaptosomes
  • Sex Characteristics
  • Rats
  • Quinpirole
  • Psychiatry
  • Male
  • Haloperidol
  • Female
  • Electrochemistry
 

Citation

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Walker, Q. D., Ray, R., & Kuhn, C. M. (2006). Sex differences in neurochemical effects of dopaminergic drugs in rat striatum. Neuropsychopharmacology, 31(6), 1193–1202. https://doi.org/10.1038/sj.npp.1300915
Walker, Q David, Rupa Ray, and Cynthia M. Kuhn. “Sex differences in neurochemical effects of dopaminergic drugs in rat striatum.Neuropsychopharmacology 31, no. 6 (June 2006): 1193–1202. https://doi.org/10.1038/sj.npp.1300915.
Walker QD, Ray R, Kuhn CM. Sex differences in neurochemical effects of dopaminergic drugs in rat striatum. Neuropsychopharmacology. 2006 Jun;31(6):1193–202.
Walker, Q. David, et al. “Sex differences in neurochemical effects of dopaminergic drugs in rat striatum.Neuropsychopharmacology, vol. 31, no. 6, June 2006, pp. 1193–202. Pubmed, doi:10.1038/sj.npp.1300915.
Walker QD, Ray R, Kuhn CM. Sex differences in neurochemical effects of dopaminergic drugs in rat striatum. Neuropsychopharmacology. 2006 Jun;31(6):1193–1202.
Journal cover image

Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

June 2006

Volume

31

Issue

6

Start / End Page

1193 / 1202

Location

England

Related Subject Headings

  • Time Factors
  • Synaptosomes
  • Sex Characteristics
  • Rats
  • Quinpirole
  • Psychiatry
  • Male
  • Haloperidol
  • Female
  • Electrochemistry