Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.

Abnormal dopaminergic neurotransmission in the hippocampus may be involved in certain aspects of cognitive dysfunction. In the hippocampus, there is l

Background: Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent.Methods: A validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age‐matched alcohol‐naïve control rats. Reverse transcriptase quantitativePCRwas used to quantify isoform‐specificDrd2gene expression levels. Using bisulfite pyrosequencing,DNAmethylation levels of a regulatory region of theDrd2gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R‐D2R, adenosine A2A receptor (A2AR)‐D2R, and sigma1 receptor (sigma1R)‐D2R.Results: Long‐term voluntary alcohol drinking significantly reducedmRNAlevels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of theDrd2gene. Alcohol drinking also reduced the striatal density of D2R‐D2R homoreceptor complexes, increased the density of A2AR‐D2R heteroreceptor complexes in theNAc shell and the dorsal striatum, and decreased the density of sigma1R‐D2R heteroreceptor complexes in the dorsal striatum.Conclusions: The present results on long‐term alcohol drinking might reflect reduced D2R levels through reductions in D2R‐D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2ARand D2R, an increased density of A2AR‐D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2R population within the complex. Hence, both reduced striatal D2R levels and reduced D2R protomer affinity within the striatal A2AR‐D2R complex might underlie reduced D2R radioligand binding in humans withAUD. This supports the hypothesis of a hypodopaminergic system inAUDand suggests the A2AR‐D2R heteroreceptor complex as a potential novel treatment target.

Illicit drug use is prevalent in the nightlife scene, especially at electronic dance music (EDM) events. The aim of the present study was to investigate illicit drug use patterns and consequences of drug use among frequent visitors of EDM events. Young adults (18–34 years old) who had visited at least six EDM events in Sweden during the past year participated in a web-based survey on drug use patterns and its consequences. Fifty-nine percent of participants had used illicit drugs during the past year, most often cannabis followed by ecstasy, cocaine, and amphetamine. Nightlife venues were identified as the main setting for the use of central stimulants, while cannabis was mostly used at home. Frequent alcohol and tobacco use was associated with illicit drug use. The most prevalent negative consequences of drug use were related to mental health, such as impairments in mood, sleep, and memory problems, but physical manifestations were also reported, such as palpitations and collapsing. These findings confirm that drug use is prevalent and associated with negative health effects among EDM nightlife attendees. The nightlife scene is a setting with promising potential to reach a high-risk target group with illicit drug use prevention interventions.