Pirino, B. E. | bioRxiv Science

bioRxiv2024

Pituitary adenylate cyclase-activating polypeptide (PACAP) overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats

BackgroundPituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored. MethodsAdult, female Long-Evans rats were injected in the PVT with an AAV to increase expression of PACAP or a control AAV. They were then investigated for subsequent gene and peptide levels of PACAP in the PVT; ethanol drinking and preference; sucrose drinking and preference; or locomotor activity in a novel chamber, behavior in a light-dark box, behavior in a novelty suppression of feeding test, locomotor activity in a familiar activity chamber, and behavior in a forced swim test. ResultsGene expression of PACAP was significantly increased in the PVT by four weeks after injection with the PACAP AAV, and this resulted in a specific increase in levels of PACAP-27. Rats injected with the PACAP AAV demonstrated reduced drinking and preference for ethanol under the intermittent-access procedure compared to those injected with the control AAV. In contrast, rats injected with the PACAP AAV showed no significant difference in drinking or preference for sucrose, or in any affective behavior tested, except that they spent less time swimming in the forced swim test. ConclusionsIn light of the low overall level of expression of PACAP-27 in the brain, the ability of PACAP-27 in the PVT to control ethanol drinking, with minimal effects on other motivated or affective behaviors, supports the idea that compounds related to PACAP-27 should be investigated as potential therapeutics for the treatment of alcohol use disorder.

neuroscience↗

bioRxiv2020

Kappa-opioid receptor stimulation in the nucleus accumbens shell: Differential effects across the rostro-caudal axis on dopamine transmission and affective behavior

Neural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behavior, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behavior using approach-avoidance assays. We report here that activation of KORs in the caudal NAc shell significantly inhibits dopamine release, stimulates novelty-induced rearing behavior, increases avoidance behavior, and reduces locomotor activity. In contrast, activation of KORs in the rostral NAc shell inhibits dopamine release to a lesser extent and instead increases approach behavior. Taken together, these results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and they suggest that this might be due to differences in KOR control over dopamine release.

neuroscience↗