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

Abstract

Alcohol 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 this brain region 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-related behaviors. Here, we employed a rodent operant drinking regimen that procedurally separates appetitive (e.g. seeking) and consummatory (e.g. intake) behaviors, chemogenetics, and brain region-specific microinjections, to determine if BLA-vHC circuitry influences alcohol drinking-related measures. 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 appetitive alcohol drinking-related behaviors while having no effect on consummatory measures. Sucrose seeking measures were also reduced following chemogenetic inhibition of this circuit. Taken together, these findings provide the first indication that the BLA-vHC circuit may regulate appetitive alcohol drinking-related 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. HIGHLIGHTSO_LIThe basolateral amygdala sends a monosynaptic glutamatergic projection to the ventral hippocampus C_LIO_LIInhibiting this circuit reduces anxiety-like behaviors in male Long Evans rats C_LIO_LIInhibition of this pathway also decreases operant alcohol seeking-related behaviors C_LI