Effects of voluntary alcohol drinking on corticotropin-releasing factor and preprodynorphin mRNA levels in the central amygdala of Sardinian alcohol-preferring rats

Abstract

The stress-response corticotropin-releasing factor (CRF) and dynorphin systems are critically involved in alcohol drinking and “anxiety” ”-related behaviors. Selectively bred Sardinian alcohol-preferring (sP) rats display high inherent “anxiety”-related behaviors, in comparison with their alcohol-non preferring counterpart (sNP rats). The present study was undertaken to investigate: (1) if there were genetically determined differences in basal gene expression levels of CRF, CRF-R1, preprodynorphin (ppDyn) and kappa opioid receptor (KOP-r) between sP and sNP rats; specifically, mRNA levels of the above genes were measured in the central amygdala (CeA), hypothalamus and other stress responsive and mesolimbic regions of alcohol-naive sP and sNP rats; and (2) if the above mRNA levels were altered by voluntary alcohol drinking in sP rats exposed to the standard, homecage 2-bottle “alcohol vs water” choice regimen 24 hours/day for 17 days. Higher basal CRF mRNA levels were found only in CeA of alcohol-naive sP rats, compared with sNP rats; these levels were decreased after alcohol consumption. In contrast, ppDyn mRNA levels in CeA of sP rats were increased by alcohol consumption, but with no basal difference from sNP rats. Although higher basal ppDyn mRNA levels were found in hypothalamus of sP rats, compared with sNP rats, there was no alteration after alcohol drinking in sP rats. No difference for the above mRNA levels was observed in other regions, including nucleus accumbens shell or core, caudate-putamen, ventral tegmental area and medial/basolateral amygdala, between the two rat lines before or after alcohol consumption. Our results demonstrate the existence of genetically determined high basal CRF mRNA levels in CeA of sP rats. Alcohol consumption decreased CeA CRF mRNA levels with parallel increases in CeA ppDyn mRNA levels.

Alcohol: A stimulant activating brain stress responsive systems with persistent neuroadaptation

“…The central nucleus of amygdala is a critical brain region mediating anxiety-related behavior, and is a likely site for the interaction of the dynorphin and alcohol, although few studies have explored this interaction. Our recent study provides further evidence for the involvement of the dynorphin system in the central nucleus of amygdala in alcohol drinking (Zhou et al, 2013c). In fact, in sP rats after large amount of alcohol consumption, there was an increase in Dyn mRNA levels in the central nucleus of amygdala, but not in any mesolimbic regions examined (nucleus accumbens shell, core) and caudate-putamen.…”

Interaction of CRF and Kappa Opioid Systems on GABAergic Neurotransmission in the Mouse Central Amygdala

“…The characteristics of reciprocal CRF-KOR interactions could be compensatory or regulatory. Zhou et al (2013) reported differential ethanol regulation of CRF and dynorphin mRNA levels: chronic ethanol decreased CRF mRNA but increased dynorphin mRNA. Therefore, the functional significance of these CRF-KOR interactions could result from different permutations of responses to their combination.…”

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…In fact, in sP rats after large amount of alcohol drinking, an increase in dynorphin mRNA levels is found in the CeA. Therefore, the KOP-r/dynorphin involved in neuronal structures related to stress responsivity (e.g., CeA) is activated after high levels of alcohol consumption in sP rats [Zhou et al, 2013c]. It is further confirmed that there are increases in dynorphin peptide levels and KOP-r signaling in the CeA of alcohol-dependent Wistar rats (induced by chronic intermittent alcohol vapor exposure) [Kissler et al, 2014].…”

“…In support of this concept, the dynorphin levels and KOP-r activity are found to be increased in the rat CeA after chronic alcohol exposure [D'Addario et al, 2013;Zhou et al, 2013c;Kissler et al, 2014]. Indeed, preclinical studies have demonstrated that the activation of p38 MAPK to stress-mediated dynorphin/KOP-r stimulation is linked to the beta-arrestin mediated transduction pathway [Bruchas et al, 2006[Bruchas et al, , 2010.…”