Haloperidol treatment reverses behavioural and anatomical changes in cocaine-dependent mice

Abnormal dopamine (DA) transmission occurs in many pathological conditions, including drug addiction. Previously, we showed DA D2 receptor (D2R) activation results in pruning of the axonal arbour of DA neurones that innervate the dorsal striatum. Thus, we hypothesised that long-term D2R stimulation through drugs of addiction should cause arbour pruning of neurones that innervate the ventral striatum and thus reduce DA release and contribute to craving. If so, D2R blockade should return these arbours to normal size and may overcome craving. We show that long-term treatment with a D2R antagonist (haloperidol) reverses behavioural and anatomical effects of cocaine dependence in mice, including relapse. This change in arbour size reflects new synapse formation and our data suggest this must occur in the presence of increased DA activity to reverse cocaine-seeking behaviour. These findings hold significant implications for the understanding and treatment of cocaine addiction.