Typical and atypical antipsychotic drugs target dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa and neurotensin-containing neurons, but not GABAergic interneurons in the shell of nucleus accumbens of ventral striatum

Specific neurons in the brain are the primary targets of the action of antipsychotic drugs. Identification and characterization of the nature of these neurons are important for understanding how antipsychotic drugs produce their effects. In previous studies GABAergic/dynorphinergic neurons were identified as a principal cell target of antipsychotic drugs in the shell of nucleus accumbens. In the present study, we further characterized which subpopulations of GABAergic neurons in this area respond after acute administration of antipsychotic drugs. Rats were treated with the typical antipsychotic haloperidol, or the prototype atypical antipsychotic clozapine and killed two hours after treatment. In appropriate sections of brain, double immunofluorescence labeling was performed with antibodies directed against markers specific to candidate cell types and Fos-like proteins (a marker to identify drug-induced cell activation). We reported here that haloperidol- and clozapine-activated neurons showed the following features: 1) approximately 54–57% of them express dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa (a marker for GABAergic medium spiny projection neurons), 2) they appear rarely to be GABAergic interneurons, marked by the calcium binding proteins, parvalbumin, calretinin or calbindin-D28K, 3) about 84–86% of them express the neuropeptide neurotensin (a neurotransmitter most often associated with projection neurons in the site tested). The results suggest that most of the antipsychotic drug–activated neurons in the shell of nucleus accumbens are likely to be neurotensin containing projection neurons.