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Rationale: The endogenous opioid and corticotropin-releasing hormone (CRH) systems, present in the central amygdala (CeA), are implicated in alcohol consumption. Objectives: The purpose of this study is to investigate the hypothesis that, in CeA, alcohol stimulates CRH release, which then stimulates β-endorphin release. Materials and methods: Rats were unilaterally implanted with a guide cannula to aim microdialysis probes in CeA. Experiment 1: rats received an intraperitoneal (IP) injection of various ethanol doses (0.0, 2.0, 2.4, or 2.8 g ethanol/kg body weight) and microdialysates were sampled at 30-min intervals to determine the effects over time of acute alcohol on the extracellular CRH concentrations in CeA. Experiment 2: phosphate-buffered saline, CRH, or CRH receptor (CRHR) antagonists (antalarmin or anti-sauvagine-30) was microinjected into CeA followed by a saline or 2.8 g/kg ethanol IP injection to determine the effects of CRHR activation or blockade in CeA on the basal and alcohol-stimulated release of β-endorphin. CRH and β-endorphin dialysate contents were determined using specific radioimmunoassays. Results: Acute alcohol induced a delayed increase in the extracellular CRH levels in CeA. Behavioural data showed no difference in locomotion between alcohol- and saline-treated rats. However, a transient increase in grooming was observed which did not correspond with alcohol-induced changes in CRH. Local CRH microinjections increased the extracellular β-endorphin concentrations in CeA. CRHR1 and CRHR2 blockade with microinjections of antalarmin and anti-sauvagine-30, respectively, attenuated the alcohol-induced increase of extracellular β-endorphin in CeA. Conclusions: Acute alcohol exerts indirect actions on CRH release and induced interactions of the CRH and β-endorphin systems in CeA. [ABSTRACT FROM AUTHOR]

Abstract: Neurons in the central amygdala (CeA) co-express dynorphin and corticotropin-releasing hormone (CRH). Moreover, the activity of both the CRH and dynorphin systems in CeA is altered by alcohol treatments, effects suggesting interactions between the CRH and dynorphin systems. Thus, the objectives of the present study were to investigate the effects of (1) activating CRH receptors (CRHRs) by microinjection of CRH in CeA and (2) blocking CRHRs by local microinjections of CRHR antagonists in the CeA on the alcohol-induced changes in the extracellular concentrations of dynorphin A1-8 with in vivo microdialysis experiments. Microdialysis probes with a microinjection port were implanted in the CeA of alcohol-naïve Sprague–Dawley rats. Microinjections of CRH or antalarmin, a CRH receptor type 1 (CRHR1) antagonist, or anti-sauvagine-30, a CRH receptor type 2 (CRHR2) antagonist, at the level of CeA were followed by an intraperitoneal injection of either saline or 2.8g ethanol/kg body weight. The content of dynorphin A1-8 was determined in dialyzate samples obtained prior to and following the various treatments using a specific radioimmunoassay. Activation of CRHRs in CeA induced an increase in the extracellular concentrations of dynorphin A1-8. Moreover, acute alcohol administration increased the extracellular concentrations of dynorphin A1-8 in CeA, an effect that was attenuated by blocking CRHR2 with anti-sauvagine-30 microinjection but not blocking CRHR1 with antalarmin microinjection. Therefore, the findings suggest an interaction between the CRH and dynorphin A1-8 systems at the level of CeA in response to acute alcohol exposure. [Copyright &y& Elsevier]

There is experimental evidence that indicates that the endogenous opioid system of the central nucleus of the amygdala (CeA) may mediate some of the reinforcing effects of ethanol. However, the precise interactions of ethanol with the endogenous opioid system at the level of the CeA have not been investigated. The aim of the current study was to investigate the hypothesis that acute systemic ethanol administration will increase the release of endogenous opioid peptides at the level of the CeA in a time- and dose-dependent manner. Rats were implanted with a unilateral guide cannula to aim microdialysis probes at the CeA. Intraperitoneal injections of saline and various doses of ethanol (0.8, 1.6, 2.0, 2.4, and 2.8 g ethanol/kg body weight) were administered to the rats. Dialysate samples were collected at 30-min intervals at distinct time points prior to and following treatment. Radioimmunoassays specific for β-endorphin, met-enkephalin, and dynorphin A1–8 were used to determine the effect of ethanol on the content of the opioid peptides in the dialysate. We report that the 2.8-g/kg dose of ethanol induced a long-lasting increase in β-endorphin release from 60 min onwards following administration and, later, an ongoing increase in dynorphin A1–8 release. None of the ethanol doses tested elicited significant changes in dialysate met-enkephalin content compared to the saline treatment. Acute systemic ethanol administration induced a dose- and time-dependent increase in β-endorphin and dynorphin A1–8 release at the level of the CeA, which may be involved in ethanol consumption. [ABSTRACT FROM AUTHOR]