Chemogenetic inhibition of a monosynaptic projection from the basolateral amygdala to the ventral hippocampus reduces appetitive and consummatory alcohol drinking behaviors

ABSTRACTAlcohol use disorder (AUD) and anxiety/stressor disorders frequently co-occur and this dual diagnosis represents a major health and economic problem worldwide. The basolateral amygdala (BLA) is a key brain region that is known to contribute to the etiology of both disorders. Although many studies have implicated BLA hyperexcitability in the pathogenesis of AUD and comorbid conditions, relatively little is known about the specific efferent projections from the BLA that contribute to these disorders. Recent optogenetic studies have shown that the BLA sends a strong monosynaptic excitatory projection to the ventral hippocampus (vHC) and that this circuit modulates anxiety- and fear-related behaviors. However, it is not known if this pathway influences alcohol drinking. Here, we employed a rodent operant drinking regimen that procedurally separates appetitive (seeking) and consummatory (intake) behaviors, chemogenetics, and brain region-specific microinjections, to determine if BLA-vHC circuitry influences alcohol drinking-related behaviors. We first confirmed prior optogenetic findings that silencing this circuit reduced anxiety-like behaviors on the elevated plus-maze. We then demonstrated that inhibiting the BLA-vHC pathway significantly reduced both appetitive and consummatory alcohol drinking behaviors. Sucrose seeking and intake were also reduced following chemogenetic inhibition of this circuit, albeit to a lesser extent than alcohol drinking measures. Taken together, these findings provide the first indication that a BLA-vHC circuit may regulate both appetitive and consummatory alcohol drinking behaviors and add to a growing body of evidence suggesting that dysregulation of this pathway may contribute to the pathophysiology of AUD and anxiety/stressor-related disorders.HIGHLIGHTSThe basolateral amygdala sends a monosynaptic projection to the ventral hippocampusInhibiting this circuit reduces anxiety-like behaviors in male Long Evans ratsInhibition of this pathway also decreases operant alcohol drinking-related behaviors