Behavioral characteristics of olanzapine: an atypical neuroleptic.
OBJECTIVE
To assess the atypical neuroleptic properties of a novel antipsychotic agent, olanzapine (Ola).


METHODS
The action of Ola on apomorpine (Apo)-induced climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)-induced head twitch response, oxotremorine-induced tremor, and the conditioned avoidance behavior in mice were observed. The catalepsy of mice induced by Ola was also investigated. The single unit extracellular recording technique was used to compare the spontaneous firing rate changes of dopamine (DA) cells in the ventral tegmental area (VTA, A10) and the substantia nigra pars compact (SNC, A9) in rats after i.v. Ola.


RESULTS
Ola antagonized the climbing behavior (ED50 1.8 mg.kg-1, p.o.), head twitch behavior (ED50 0.3 mg.kg-1, p.o.), and tremor (ED50 5.2 mg.kg-1, p.o.) in mice. In a conditioned avoidance paradigm in mice, Ola inhibited the avoidance response with an ED50 of 2.72 mg.kg-1 (p.o.). However, the catalepsy was not induced by Ola in mice even under a very high dose of 100 mg.kg-1 (p.o.). Ola selectively increased the firing rate of DA cells in the VTA, but failed to affect that of SNC DA cells.


CONCLUSIONS
Ola distinguished itself from the typical neuroleptic (e.g. haloperidol, Hal) and took resemblance of the atypical neuroleptic (e.g. clozapine, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving D1/D2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block of conditioned avoidance response and catalepsy induction; and 3) the specificity of action sites of firing rates upon acute drug challenge.
Fu
Y
Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
Zhu
Z T
ZT
Chen
L J
LJ
Yu
L P
LP
Jin
G Z
GZ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines; D002375:Catalepsy / Q000209:etiology; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000502:physiology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine; D004298:Dopamine