Effect of the 5-HT6 receptor antagonists Ro04-6790 and Ro65-7199 on latent inhibition and prepulse inhibition in the rat: comparison to clozapine.
In the present study, we have investigated the effects of two selective 5-HT6 receptor antagonists, Ro04-6790 and Ro65-7199, in three drug-induced models of PPI disruption and on latent inhibition (LI) utilizing a conditioned lick suppression (CLS) procedure. Clozapine was included in each experiment for comparison. Neither Ro04-6790 nor Ro65-7199 (both 30 mg/kg) affected the PPI disruption produced by PCP (1.5 mg/kg s.c.), apomorphine (0.1 mg/kg s.c.), or LSD (0.1 mg/kg s.c.). There was also no interaction between each drug and CS preexposure in the CLS test indicating a failure of each drug to facilitate LI. In contrast, clozapine (12 mg/kg) attenuated an apomorphine and PCP-induced PPI deficit, although the PPI disruption produced by LSD was not significantly affected. At a lower dose of 5 mg/kg, clozapine also facilitated LI. Since each of these tests bear some predictive validity for the detection of antipsychotic drugs, the present studies do not support a therapeutic potential of 5-HT6 receptor antagonists in this regard.
Leng
Andreas
A
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland.
Ouagazzal
Abdel
A
Feldon
Joram
J
Higgins
Guy A
GA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000109:Acetylcholine; D014150:Antipsychotic Agents; D001058:Apomorphine; D003024:Clozapine; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D008238:Lysergic Acid Diethylamide; D010622:Phencyclidine; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C114163:Ro 4-6790; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor