MDL 73,147EF, a 5-HT3 antagonist, facilitates latent inhibition in the rat.
Latent inhibition (LI) is a behavioral model of selective attention that has been used to study the attentional deficits seen in schizophrenia. In the present study, we examined the effect of 5-hydroxytryptamine3 (5-HT3) receptor blockade on LI using the conditioned emotional response (CER) procedure. Prior exposure to 20, 30, or 40 stimulus presentations significantly, and almost completely, inhibited the CER to that stimulus. This LI effect was much weaker when only 10 preexposures were given. 1H-indole-3-carboxylic acid, trans-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl ester methanesulfonate (MDL 73,147EF), a selective 5-HT3 receptor antagonist, significantly facilitated the LI effect observed after 10 preexposures at 0.1 mg/kg but not at 0.01 mg/kg. The magnitude of this effect was comparable to that observed with the classical neuroleptic haloperidol (0.1 mg/kg). Neither MDL 73,147EF nor haloperidol affected the CER in animals not preexposed to the stimulus. These results strongly corroborate suggestions that 5-HT3 receptor antagonists will be of use in the treatment of schizophrenia.
Moran
P M
PM
Marion Merrell Dow Research Institute, Strasbourg, France.
Moser
P C
PC
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004597:Electroshock; D004644:Emotions / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists
D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron; D006220:Haloperidol