Enhancement of antipsychoticlike properties of raclopride in rats using the selective serotonin2A receptor antagonist MDL 100,907.
BACKGROUND
Selective suppression of conditioned avoidance response (CAR) is a standard animal screening test for predicting antipsychotic effect. Ability to suppress CAR is presumed to be due to antagonism at dopamine receptors, a property shared by all known antipsychotics.


METHODS
Using CAR behavior, in a conventional shuttle-box paradigm, as an index for antipsychotic efficacy, the effects of the selective serotonin2A receptor antagonist MDL 100,907 alone, and in combination with the dopamine D2 receptor antagonist raclopride, were studied in adult male Sprague-Dawley rats. Nonparametric procedures were employed for statistical evaluation.


RESULTS
MDL 100,907 (0.1-1.5 mg/kg, SC) alone did not suppress CAR in a manner predictive of antipsychotic activity; however, in the presence of an ED50 (0.14 mg/kg, SC) dose of raclopride, MDL 100,907 enhanced and prolonged the suppression of CAR. In the presence of a subthreshold (0.05 mg/kg, SC) dose of raclopride, MDL 100,907 induced a suppression of CAR.


CONCLUSIONS
The results suggest that treatment with a selective serotonin2A receptor antagonist alone may not produce a robust antipsychotic effect; however, a selective serotonin2A receptor antagonist in the presence of a minimal dopamine D2 receptor blocking action could potentially be an adjunctive therapy resulting in improved antipsychotic efficacy and fewer extrapyramidal symptoms.
Department of Psychiatry, Scott & White Clinic Temple, Texas, USA.
M L
ML
Wadenberg
P B
PB
Hicks
J T
JT
Richter
K A
KA
Young
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005464:Fluorobenzenes / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D014150:Antipsychotic Agents; D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012457:Salicylamides; D012702:Serotonin Antagonists; D020891:Raclopride; C079049:volinanserin