Sex-specific responses on alcohol intake in rodents following sCT infusion in the middle part of the paraventricular nucleus of the thalamus

BACKGROUND: Long-term alcohol consumption contributes to the development of alcohol use disorder (AUD), a complex disorder with multifaceted neurobiological underpinnings. One of these is appetite-regulatory peptides, such as amylin, where activation of the amylin receptor (AMYR) suppresses alcohol-related behaviours in rodents. Earlier research has pinpointed AMYR in the nucleus accumbens (NAc) as central for this interaction, where other brain regions most likely participate. One of these might be the middle part of the paraventricular thalamus (mid-PVT), a critical node in reward-related processes. We therefore accessed this interaction through a combination of behavioural, neurochemical, and molecular experiments. METHODS: Western Blot, immunohistochemistry, and RNAscope were utilized to identify the calcitonin receptor (CTR), the main component of AMYR, in mid-PVT. To investigate the effects of salmon calcitonin (sCT), a CTR and AMYR agonist, locally infused in the mid-PVT on alcohol-related behaviours in rodents, the intermittent alcohol drinking paradigm, locomotor stimulation test, and microdialysis setup were employed. FINDINGS: CTR was detected in the thalamus in male NMRI mice and in mid-PVT of Wistar and Sprague Dawley (SD) rats. Locally infused sCT into mid-PVT decreased alcohol intake in males (P = 0.0048), but not in female (P = 0.8982) Wistar rats. A pilot experiment indicated that CTR was co-localized with glutamatergic projections from mid-PVT to NAc in males, but not female SD rats. Moreover, in male NMRI mice, sCT into mid-PVT attenuated alcohol-induced locomotor stimulation and dopamine release in NAc. INTERPRETATION: In summary, sCT into mid-PVT suppressed alcohol-related behaviours in male rodents, potentially through CTR on glutamatergic projections to NAc.