LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs

The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms.