Combined 5-HT2/D-2 receptor blockade inhibits the firing rate of SNR neurons in the rat brain

1. The aim of the present study was to evaluate the contribution of seroton in (5-HT) and dopamine (DA) receptor antagonism to the distinct inhibitory effects of the atypical antipsychotics clozapine and risperidone on SNR neu rons, we have shown previously. 2. Utilizing extracellular recordings in the SNR in chloral hydrate anaesth etized rats, raclopride, a selective DA D-2/D-3 receptor antagonist and LY 53857, a 5-HT2A/2C receptor antagonist were studied separately and in combi nation for their effects on the firing rate of the SNR neurons. 3. Both raclopride and LY 53857 induced a slight but significant increase i n the firing rate of the SNR neurons in a limited dose range. 4. Upon pretreatment with a single dose of raclopride, LY 53857 induced a d ose-dependent inhibitory effect on the firing rate of the SNR neurons. 5. Concurrent 5-HT2 and moderate DA D-2 receptor antagonism can mimic the i n vivo effects of the atypical antipsychotics clozapine and risperidone on the firing rate of SNR neurons.