Abstract
Alcohol causes stimulatory behavioral responses by activating reward-processing brain areas including the laterodorsal (LDTg) and ventral tegmental areas (VTA) and the nucleus accumbens (NAc). Systemic administration of the amylin and calcitonin receptor agonist salmon calcitonin (sCT) attenuates alcohol-mediated behaviors, but the brain sites involved in this process remain unknown. Firstly, to identify potential sCT sites of action in the brain, we used immunohistochemistry after systemic administration of fluorescent-labeled sCT. We then performed behavioral experiments to explore how infused sCT into the aforementioned reward-processing brain areas affects acute alcohol-induced behaviors in mice and chronic alcohol consumption in rats. We show that peripheral sCT crosses the blood brain barrier and is detected in all the brain areas studied herein. sCT infused into the LDTg attenuates alcohol-evoked dopamine release in the NAc shell in mice and reduces alcohol intake in rats. sCT into the VTA blocks alcohol-induced locomotor stimulation and dopamine release in the NAc shell in mice and decreases alcohol intake in rats. Lastly, sCT into the NAc shell prevents alcohol-induced locomotor activity in mice. Our data suggest that central sCT modulates the ability of alcohol to activate reward-processing brain regions.
Highlights
The stimulatory behavioral responses caused by alcohol are attrib uted to its ability to activate various brain areas processing reward, such as the laterodorsal tegmental area (LDTg), ventral tegmental area (VTA) and nucleus accumbens (NAc) shell (for review see (Engel and Jerlhag, 2014; Jayaram-Lindstrom et al, 2016; Soderpalm and Ericson, 2013))
Our immunohistochemical results show that peripheral fluorescein amidite (FAM)-labeled salmon calcitonin (sCT) penetrates the brain and reaches reward-processing areas, including the LDTg, ventral tegmental areas (VTA) and NAc
The present behavioral ex periments further reveal that locally administered sCT into either the LDTg, VTA or NAc shell modulates various acute and chronic alcohol-mediated behaviors in male rodents
Summary
The stimulatory behavioral responses caused by alcohol are attrib uted to its ability to activate various brain areas processing reward, such as the laterodorsal tegmental area (LDTg), ventral tegmental area (VTA) and nucleus accumbens (NAc) shell (for review see (Engel and Jerlhag, 2014; Jayaram-Lindstrom et al, 2016; Soderpalm and Ericson, 2013)). These behavioral outcomes of alcohol are closely linked both to direct local activation of the aformentioned areas and to increased activity in these systems (Engleman et al, 2009; Jerlhag and Engel, 2014; Larsson et al, 2005, 2002). Despite the advantages of sCT in activating the amylin signaling
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