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Evidence for the involvement of ERbeta and RGS9-2 in 17-beta estradiol enhancement of amphetamine-induced place preference behavior.

ABSTRACT: Estrogen enhances dopamine-mediated behaviors, which make women and female rats more sensitive to the effects of the psychostimulant drugs, cocaine and amphetamine. How cocaine and amphetamine elicit more robust behavioral responses in females remains unclear, but studies have shown that the Regulator of G-protein Signaling 9-2 (RGS9-2) protein is an important modulator of the behavioral responses to these drugs. Previously, we reported that 17-beta estradiol reduced RGS9-2 mRNA expression in the shell of the nucleus accumbens, but not the core. The present studies were designed to further evaluate the involvement of RGS9-2 in estradiol enhancement of amphetamine-induced place preference behavior and to examine which estrogen receptor subtype mediates the effect of estradiol. Female Sprague-Dawley rats were ovariectomized and treated for 14 days with an inert vehicle or 17-beta estradiol (by Silastic implant or injection [80 microg/kg]). 17-beta-Estradiol-treated female rats had enhanced amphetamine-induced conditioned place preference behavior compared to vehicle-treated, ovariectomized female rats. In situ hybridization histochemistry and Western blotting identified an inverse relationship between RGS9-2 protein expression in the nucleus accumbens shell and the hormonal enhancement of amphetamine-induced place preference behavior. A similar relationship was not found between place preference behavior and RGS9-2 expression in the accumbens core. Moreover, treatment of ovariectomized female rats with the selective estrogen receptor-beta agonist, diarylpropionitrile (1 mg/kg), for 2 weeks also facilitated amphetamine-induced place preference behavior and selectively reduced nucleus accumbens shell RGS9-2 protein expression. These data provide insight into a potential mechanism by which estrogen and/or sex modulate mesoaccumbal dopamine receptor signaling and possibly, addictive behaviors.

SUBMITTER: Silverman JL

PROVIDER: S-EPMC2096711 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Evidence for the involvement of ERbeta and RGS9-2 in 17-beta estradiol enhancement of amphetamine-induced place preference behavior.

Silverman Jill L JL Koenig James I JI

Hormones and behavior 20070331 2

Estrogen enhances dopamine-mediated behaviors, which make women and female rats more sensitive to the effects of the psychostimulant drugs, cocaine and amphetamine. How cocaine and amphetamine elicit more robust behavioral responses in females remains unclear, but studies have shown that the Regulator of G-protein Signaling 9-2 (RGS9-2) protein is an important modulator of the behavioral responses to these drugs. Previously, we reported that 17-beta estradiol reduced RGS9-2 mRNA expression in th ...[more]

PMID: 17493623

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Project description:Symptoms of the dopamine dysregulation syndrome in patients with Parkinsonâs disease (PD) are close to those observed in psychostimulant addiction. This suggests that dopamine replacement therapy shares some properties with potentially addictive drugs. A remaining challenge is to understand the neuroadaptations leading to compulsive dopaminergic medication use. To this end, the reinforcing properties of the D2/D3 agonist pramipexole (PPX) were assessed after chronic exposure to L-dopa in an alpha-synuclein PD rat model. Individual male rats underwent a bilateral nigral loss induced by AAV-mediated alpha-synuclein overexpression. Control sham animals received stereotaxic injection of the same AAV vector enabeling expresion of the GFP. Five weeks after lesion induction, animals received a subcutaneous daily administration of L-dopa methyl-ester (50mg/kg) plus benserazide (12,5mg/kg) or a saline solution. Following this 3 weeks period of chronic treatment, the reinforcing properties of the D2/D3 agonist pramipexole were assessed using a place conditioning paradigm. This procedure consists in pairing a drug with a specific environment and vehicle with another environment during a conditioning period. The first day, animals received an intraperitoneal injection of saline solution before a 20min habituation period that allowed exploration of the apparatus (pre-test). Time spent in each chamber was analyzed. The compartment less occupied by the animal was determined as the drug paired side. The following days, animals received either pramipexole 2mg/kg on days 1, 3, 5 and 7 or vehicle on days 2, 4, 6 and 8 and were placed in the paired-chamber for 40 minutes. Controls groups received saline solution during all conditioning sessions. The day following the last conditioning session, a probe test (post test) was performed with 20min free access to the apparatus after an ip injection of saline solution. Place preference scores were calculated as the difference in time spent in the drug-paired chamber between post-test and pre-test.

Dataset Information

Evidence for the involvement of ERbeta and RGS9-2 in 17-beta estradiol enhancement of amphetamine-induced place preference behavior.

Publications

Evidence for the involvement of ERbeta and RGS9-2 in 17-beta estradiol enhancement of amphetamine-induced place preference behavior.

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