Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5

Luis A. Martinez, Kellie S. Gross, Brett T. Himmler, Nicole L. Emmitt, Brittni M. Peterson, Natalie E. Zlebnik, Michael Olive, Marilyn E. Carroll, Robert L. Meisel, Paul G. Mermelstein

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In comparison to men, women initiate drug use at earlier ages and progress from initial use to addiction more rapidly. This heightened intake and vulnerability to drugs of abuse is regulated in part by estradiol, although the signaling mechanisms by which this occurs are not well understood. Recent findings indicate that within the nucleus accumbens core, estradiol induces structural plasticity via membrane-localized estrogen receptor _, functionally coupled to metabotropic glutamate receptor subtype 5 (mGluR5). Hence, we sought to determine whether mGluR5 activation was essential for estradiolmediated enhancement of cocaine self-administration. Ovariectomized (OVX) female rats were allowed to freely selfadminister cocaine under extended access conditions (6 h/d) for 10 consecutive days. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) or vehicle was administered before estradiol (or oil), on a 2 d on/2 d off schedule throughout the extended access period. MPEP treatment prevented the estradiol-dependent enhancement of cocaine self-administration in OVX females. In a separate experiment, potentiation of mGluR5 function with the positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (in the absence of estradiol treatment) failed to increase cocaine self-administration. These data suggest that mGluR5 activation is necessary for estradiol-mediated enhancement of responses to cocaine, but that direct mGluR5 activation is insufficient to mimic the female response to estradiol. Building on previous studies in male animals, these findings further highlight the therapeutic potential of mGluR5 antagonism in the treatment of addiction and suggest that there may be added therapeutic benefit in females.

Original languageEnglish (US)
Article numbere0140-16.2016
JournaleNeuro
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Metabotropic Glutamate 5 Receptor
Self Administration
Cocaine
Estradiol
Therapeutics
Nucleus Accumbens
Street Drugs
Estrogen Receptors
Appointments and Schedules
Oils
Membranes

Keywords

  • Drug addiction
  • Estrogen
  • Glutamate
  • Nucleus accumbens
  • Plasticity
  • Psychostimulant

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Martinez, L. A., Gross, K. S., Himmler, B. T., Emmitt, N. L., Peterson, B. M., Zlebnik, N. E., ... Mermelstein, P. G. (2016). Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5. eNeuro, 3(5), [e0140-16.2016]. https://doi.org/10.1523/ENEURO.0140-16.2016

Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5. / Martinez, Luis A.; Gross, Kellie S.; Himmler, Brett T.; Emmitt, Nicole L.; Peterson, Brittni M.; Zlebnik, Natalie E.; Olive, Michael; Carroll, Marilyn E.; Meisel, Robert L.; Mermelstein, Paul G.

In: eNeuro, Vol. 3, No. 5, e0140-16.2016, 01.09.2016.

Research output: Contribution to journalArticle

Martinez, LA, Gross, KS, Himmler, BT, Emmitt, NL, Peterson, BM, Zlebnik, NE, Olive, M, Carroll, ME, Meisel, RL & Mermelstein, PG 2016, 'Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5', eNeuro, vol. 3, no. 5, e0140-16.2016. https://doi.org/10.1523/ENEURO.0140-16.2016
Martinez LA, Gross KS, Himmler BT, Emmitt NL, Peterson BM, Zlebnik NE et al. Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5. eNeuro. 2016 Sep 1;3(5). e0140-16.2016. https://doi.org/10.1523/ENEURO.0140-16.2016
Martinez, Luis A. ; Gross, Kellie S. ; Himmler, Brett T. ; Emmitt, Nicole L. ; Peterson, Brittni M. ; Zlebnik, Natalie E. ; Olive, Michael ; Carroll, Marilyn E. ; Meisel, Robert L. ; Mermelstein, Paul G. / Estradiol facilitation of cocaine Self-Administration in female rats requires activation of mglur5. In: eNeuro. 2016 ; Vol. 3, No. 5.
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