Combined 5-HT2/D2 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 serotonin (5-HT) and dopamine (DA) receptor antagonism to the distinct inhibitory effects of the atypical antipsychotics clozapine and risperidone on SNR neurons, we have shown previously. 2. Utilizing extracellular recordings in the SNR in chloral hydrate anaesthetized rats, raclopride, a selective DA D2/D3 receptor antagonist and LY 53857, a 5-HT2A:2c receptor antagonist were studied separately and in combination for their effects on the firing rate of the SNR neurons. 3. Both raclopride and LY 53857 induced a slight but significant increase in 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 dose-dependent inhibitory effect on the firing rate of the SNR neurons. 5. Concurrent 5-HT2 and moderate DA D2 receptor antagonism can mimic the in vivo effects of the atypical antipsychotics clozapine and risperidone on the firing rate of SNR neurons.
Bruggeman
R
R
Department of Medicinal Chemistry, University Center for Pharmacy, Academic Hospital Groningen, The Netherlands. r.bruggeman@farm.rug.nl
Heeringa
M
M
Westerink
B H
BH
Timmerman
W
W
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D003024:Clozapine / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D003024:Clozapine; D018967:Risperidone