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Cortisol/corticosterone and the hypothalamic-pituitary-adrenal (HPA) axis serve an important role in modulating alcohol drinking behaviors. To date most alcohol research has focused on the functional involvement of corticosterone and the glucocorticoid receptor (GR), the primary receptor for corticosterone. Recent studies have indicated that the related mineralocorticoid receptor (MR), which binds both corticosterone and aldosterone, may also play a role in alcohol drinking. Therefore, the purpose of the present study was to test the functional role of MR signaling in alcohol self-administration via pharmacological antagonism of the MR with spironolactone. Male and female Long-Evans rats were trained to self-administer a sweetened alcohol solution (15% (v/v) alcohol +2% (w/v) sucrose). The effects of spironolactone (0, 10, 25, 50 mg/kg; IP) were tested on alcohol self-administration and under "probe extinction" conditions to measure the persistence of responding in the absence of the alcohol reinforcer. Parallel experiments in sucrose self-administration trained rats were used to confirm the specificity of spironolactone effects to an alcohol reinforcer. In female rats spironolactone (50 mg/kg) reduced alcohol self-administration and persistence of alcohol responding. In male rats spironolactone (25 and 50 mg/kg) reduced alcohol self-administration, but not persistence of alcohol responding. Spironolactone reduced sucrose intake in female rats only, and locomotion in male and female rats during sucrose self-administration. There was no effect of spironolactone on persistence of sucrose responding. These studies add to growing evidence that the MR is involved in alcohol drinking, while underscoring the importance of studying both male and female animals.
This article was published in the following journal.
Name: Pharmacology, biochemistry, and behavior
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Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.
A thiazole derivative and atypical ANTIPSYCHOTIC AGENT that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST; SEROTONIN 5-HT2 RECEPTOR ANTAGONIST, serotonin 5-HT7 receptor antagonist, and antagonist of the adrenergic α2A and α2C receptors, as well as a partial SEROTONIN 5-HT1A RECEPTOR AGONIST. It is used in the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER.
A benzisoxazole derivative and active metabolite of RISPERIDONE that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST and SEROTONIN 5-HT2 RECEPTOR ANTAGONIST. It is an ANTIPSYCHOTIC AGENT used in the treatment of SCHIZOPHRENIA.
A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.
A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.
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