Major depressive disorder (MDD) is a challenging psychiatric problem with variation in symptoms and response to treatment. It remains a common and under-treated illness, resulting in a high degree of disability and mortality worldwide. It is also intriguing to note the higher prevalence of MDD in women than men. To this end, we are examining if there are any gender-specific differences in signaling pathways mainly endocannabinoid system associated with depressive behavior. The other area of our research actively being perused is to understand the neurochemical mechanisms of alcohol abuse disorder (reward, tolerance, dependence and relapse). Our laboratory is also interested in examining the neurochemical and behavioral effects of gestational cannabis and alcohol exposure on offspring. To achieve these goals, we utilize rodent models (mouse and rat) and human postmortem brains, and employ various biochemical, genetic, behavioral, and pharmacological approaches. Our long-term aim is to develop effective therapeutic interventions through understanding of molecular mechanisms underlying these disorders.