Nicotine is the main addictive component in cigarettes. After chronic exposure to nicotine, neural adaptations in key brain areas lead to an aversive state upon withdrawal from nicotine consumption. This withdrawal state is accompanied by unpleasant behavioral manifestations that increases susceptibility to nicotine relapse. These withdrawal symptoms encompass somatic and affective components. These negative symptoms are associated with activity in the interpeduncular nucleus (IPN), a midbrain structure that increases activity with presentation of aversive stimuli, including aversion to high doses of nicotine and withdrawal from chronic nicotine. While it has been shown that the IPN mediates negative effects of nicotine withdrawal, how the IPN mediates this aversive state through the efferent connections to downstream targets has not been clearly elucidated. Based on previous studies in the lab, activation of inhibitory GABAergic connections from the IPN to the laterodorsal tegmentum (LDTg) is aversive and silencing these projections prevents aversive response to an acute high dose of nicotine in mice. We hypothesize that the GABAergic projections from IPN to LDTg are recruited during withdrawal from chronic nicotine promoting an aversive state and withdrawal symptoms. This thesis explores the use optogenetics for control over circuit activation and inhibition to study its contribution to nicotine withdrawal behavior and physiology. By studying the IPN to LDTg circuit in the context of nicotine withdrawal we may elucidate areas with novel drug targets, which have therapeutic potential to relieve nicotine withdrawal symptoms and improve cessation outcomes.