Behavioral characteristics of olanzapine: an atypical neuroleptic

AIM: To assess the atypical neuroleptic properties of a novel antipsychotic agent, olanzapine (Ola). METHODS: The action of Ola on apomorpine (Apo)-in duced climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)induced head twitch response, oxotremorine-induced tremor, and the conditioned avoidance behav ior in mice were observed. The catalepsy of mice induced by Ola was also in vestigated. The single unit extracellular recording technique was used to c ompare the spontaneous firing rate changes of dopamine (DA) cells in the ve ntral tegmental area (VTA, A(10)) and the substantia nigra pars compact (SN C, A(9)) in rats after iv Ola. RESULTS: Ola antagonized the climbing behavi or (ED50 18 mg.kg(-1), po), head twitch behavior (ED50 0.3 mg.kg(-1) po), a nd tremor (ED50 5.2 mg.kg(-1), po) in mice. In a conditioned avoidance para digm in mice, Ola inhibited the avoidance response with an ED50 of 2.72 mg. kg(-1) (po). However, the catalepsy was not induced by Ola in mice even und er a very high dose of 100 mg.kg(-1) (po). Ola selectively increased the fi ring rate of DA cells in the VTA, but failed to affect that of SNC DA cells . CONCLUSION: Ola distinguished itself from the typical neuroleptic leg hal operidol, Hall and took resemblance of the atypical neuroleptic (eg clozapi ne, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving D-1/D-2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block of conditioned avoidance response and catalepsy induction; and 3) th e specificity of action sites of firing rates upon acute drug challenge.