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. 2013 Apr;24(2):95-104.
doi: 10.1097/FBP.0b013e32835efc5f.

Ovarian hormones and the heterogeneous receptor mechanisms mediating the discriminative stimulus effects of ethanol in female rats

Christa M Helms  1 , Aubrey D McCracken, Sharon L Heichman, Travis M Moschak
Affiliations

Ovarian hormones and the heterogeneous receptor mechanisms mediating the discriminative stimulus effects of ethanol in female rats

Christa M Helms et al. Behav Pharmacol. 2013 Apr.

Abstract

Past studies have suggested that progesterone-derived ovarian hormones contribute to the discriminative stimulus effects of ethanol, particularly via progesterone metabolites that act at γ-aminobutyric acid type A (GABA(A)) receptors. It is unknown whether loss of ovarian hormones in women, for example, after menopause, may be associated with altered receptor mediation of the effects of ethanol. The current study measured the substitution of allopregnanolone, pregnanolone, pentobarbital, midazolam, dizocilpine, TFMPP, and RU 24969 in female sham and ovariectomized rats trained to discriminate 1.0 g/kg ethanol from water. The groups did not differ in the substitution of GABA(A)-positive modulators (barbiturates, benzodiazepines, neuroactive steroids) or the N-methyl-D-aspartate receptor antagonist dizocilpine. Similarly, blood-ethanol concentration did not differ between the groups, and plasma adrenocorticotropic hormone, progesterone, pregnenolone, and deoxycorticosterone were unchanged 30 min after administration of 1.0 g/kg ethanol or water. However, substitution of neuroactive steroids and RU 24969, a 5-hydroxytryptamine (5-HT)(1A/1B) receptor agonist, was lower than observed in previous studies of male rats, and TFMPP substitution was decreased in ovariectomized rats. Ovarian hormones appear to contribute to 5-HT receptor mediation of the discriminative stimulus effects of ethanol in rats.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Mean (±SEM) ethanol-appropriate responding and percentage of baseline response rate (RR) by test drug dose in female sham (closed circles) and ovariectomized (open circles) rats trained to discriminate 1.0 g/kg ethanol from water. The dashed lines show the criteria for complete substitution and response rate equivalent to baseline. On average, each rat was tested with a (mean±SD) minimum of 5.5±1.5 doses and a maximum of 12.1±1.8 doses of each drug; **P<0.01. i.p. intraperitoneally.
Fig. 2
Fig. 2
Percentage of sham and ovariectomized (OVX) female rats showing complete substitution of TFMPP for 1.0 g/kg ethanol; *P<0.05.
See this image and copyright information in PMC

References

    1. Besheer J, Stevenson RA, Hodge CW. mGlu5 receptors are involved in the discriminative stimulus effects of self-administered ethanol in rats. Eur J Pharmacol. 2006;551:71–75. - PMC - PubMed
    1. Bethea CL, Smith AW, Centeno ML, Reddy AP. Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques. Neuroscience. 2011;192:675–688. - PMC - PubMed
    1. Bowen CA, Purdy RH, Grant KA. Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: effects of ethanol training dose and dosing procedure. J Pharmacol Exp Ther. 1999;289:405–411. - PubMed
    1. Boyd KN, Kumar S, O’Buckley TK, Morrow AL. Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH. J Neurochem. 2010a;115:142–152. - PMC - PubMed
    1. Boyd KN, Kumar S, O’Buckley TK, Porcu P, Morrow AL. Ethanol induction of steroidogenesis in rat adrenal and brain is dependent upon pituitary ACTH release and de novo adrenal StAR synthesis. J Neurochem. 2010b;112:784–796. - PMC - PubMed

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