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Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy.

Publication ,  Journal Article
Walker, QD; Johnson, ML; Van Swearingen, AED; Arrant, AE; Caster, JM; Kuhn, CM
Published in: Neuropharmacology
June 1, 2012

Ovarian hormones modulate the pharmacological effects of psychostimulants and may enhance vulnerability to drug addiction. Female rats have more midbrain dopamine neurons than males and greater dopamine uptake and release rates. Cocaine stimulates motor behavior and dopamine efflux more in female than male rats, but the mediating mechanisms are unknown. This study investigated individual differences in anatomic, neurochemical, and behavioral measures in female rats to understand how ovarian hormones affect the relatedness of these endpoints. Ovarian hormone effects were assessed by comparing individual responses in ovariectomized (OVX) and sham adult female rats. Locomotion was determined before and following 10mg/kg cocaine. Electrically-stimulated dopamine efflux was assessed using fast cyclic voltammetry in vivo. Dopamine neuron number and density in substantia nigra (SN) and ventral tegmental area (VTA) were determined in the same animals using tyrosine-hydroxylase immunohistochemistry and unbiased stereology. Locomotor behavior and dopamine efflux did not differ at baseline but were greater in sham than OVX following cocaine. Cocaine increased dopamine release rates in both groups but uptake inhibition (K(m)) was greater in sham than OVX. Dopamine neuron number and density in SN and VTA were greater in shams. Sham females with the largest uterine weights exhibited the highest density of dopamine neurons in the SN, and the most cocaine-stimulated behavior and dopamine efflux. Ovariectomy eliminated these relationships. We postulate that SN density could link ovarian hormones and high-psychostimulant responses in females. Similar mechanisms may be involved in individual differences in the addiction vulnerability of women. Copyright © 2012. Published by Elsevier Ltd.

Duke Scholars

Published In

Neuropharmacology

EISSN

1873-7064

Publication Date

June 1, 2012

Volume

62

Issue

7

Start / End Page

2267 / 2277

Related Subject Headings

  • Neurology & Neurosurgery
  • 1701 Psychology
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1109 Neurosciences
 

Citation

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Walker, Q. D., Johnson, M. L., Van Swearingen, A. E. D., Arrant, A. E., Caster, J. M., & Kuhn, C. M. (2012). Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy. Neuropharmacology, 62(7), 2267–2277.
Walker, Q. D., M. L. Johnson, A. E. D. Van Swearingen, A. E. Arrant, J. M. Caster, and C. M. Kuhn. “Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy.Neuropharmacology 62, no. 7 (June 1, 2012): 2267–77.
Walker QD, Johnson ML, Van Swearingen AED, Arrant AE, Caster JM, Kuhn CM. Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy. Neuropharmacology. 2012 Jun 1;62(7):2267–77.
Walker, Q. D., et al. “Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy.Neuropharmacology, vol. 62, no. 7, June 2012, pp. 2267–77.
Walker QD, Johnson ML, Van Swearingen AED, Arrant AE, Caster JM, Kuhn CM. Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy. Neuropharmacology. 2012 Jun 1;62(7):2267–2277.
Journal cover image

Published In

Neuropharmacology

EISSN

1873-7064

Publication Date

June 1, 2012

Volume

62

Issue

7

Start / End Page

2267 / 2277

Related Subject Headings

  • Neurology & Neurosurgery
  • 1701 Psychology
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1109 Neurosciences