Quetiapine (Seroquel) shows a pattern of behavioral effects similar to the atypical antipsychotics clozapine and olanzapine: studies with tremulous jaw movements in rats.
BACKGROUND
Previous studies demonstrated that clozapine and olanzapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing.


OBJECTIVE
The present studies were undertaken to evaluate the novel atypical antipsychotic quetiapine using the jaw movement model.


METHODS
The effect of acute quetiapine on the suppression of tacrine-induced tremulous jaw movements was examined. To determine the relative potency of this effect compared with other behavioral effects of quetiapine, suppression of lever pressing also was studied. In other studies, rats received quetiapine for 14 consecutive days to study the effects of repeated injections of this drug.


RESULTS
Acute quetiapine injections decreased tacrine-induced jaw movements and lever pressing. The ratio of the ED50 for suppression of jaw movements divided by the ED50 for suppression of lever pressing was used as an index of liability to produce motor side effects, and the present results demonstrate that quetiapine has a ratio similar to that previously shown for clozapine and olanzapine. In the repeated-administration studies, quetiapine failed to induce jaw movements. On day 14, quetiapine reduced tacrine-induced tremulous jaw movements, and in a parallel experiment quetiapine significantly suppressed lever pressing on days 1-14. Repeated injections of quetiapine reduced tacrine-induced jaw movements over a dose range lower than that required for suppression of lever pressing.


CONCLUSIONS
On tests of jaw movement activity and lever pressing after both acute and repeated drug administration, quetiapine showed a profile somewhat similar to clozapine and olanzapine. A theoretical model is offered suggesting that atypical antipsychotics that act on 5-HT or muscarinic receptors have intrinsic antiparkinsonian actions that work in opposition to the motor effects produced by dopamine antagonism.
Betz
A
A
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Ishiwari
K
K
Wisniecki
A
A
Huyn
N
N
Salamone
J D
JD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007568:Jaw; D008297:Male; D009068:Movement / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D013619:Tacrine / Q000494:pharmacology
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018697:Nootropic Agents; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D013619:Tacrine; D003024:Clozapine; D000077152:Olanzapine