Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit.

Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

Basolateral Amygdala Cannabinoid CB1 Receptor Controls Formation and Elimination of Social Fear Memory.

Patients with post-traumatic stress disorder (PTSD) usually manifest persistence of the traumatic memory for a long time after the event, also known as resistance to extinction learning. Numerous studies have shown that the endocannabinoid system, specifically the cannabinoid type-1 receptor (CB1R), plays an important role in traumatic memory. However, the effect of basolateral amygdala (BLA) CB1R in social fear memory formation and elimination is still unclear. Here, we built a mouse model of social avoidance induced by acute social defeat stress to investigate the role of BLA CB1R in social fear memory formation and anxiety- and depression-like behavior. Anterograde knockout of CB1R in BLA neurons facilitates social fear memory formation and manifests an anxiolytic effect but does not influence sociability and social novelty. Retrograde knockout of CB1R in BLA promotes social fear memory formation and shows an anxiogenic effect but does not affect sociability and social novelty. Moreover, intracerebral injection of the CB1R antagonist AM251 in BLA during the memory reconsolidation time window eliminates social fear memory. Our findings suggest the CB1R of BLA can be used as a novel molecular target in social fear memory formation and elimination and potential PTSD therapy with memory retrieval and AM251.