Haloperidol and loxapine but not clozapine increase synaptic responses in the hippocampus

Effects of two typical neuroleptics haloperidol and loxapine, and an atypical antipsychotic clozapine on excitatory synaptic transmission were examined in the CA1 area of rat hippocampal slices. Haloperidol (10 mumol) and loxapine (10 mumol) increased extracelllar evoked field potentials by an average of 57 and 125% of the control level respectively. Clozapine (50 mumol) induced a transient depression (21% of control) of the response followed by a small augmentation (10%). Examination of haloperidol actions using the whole cell clamp technique showed an increase in the amplitude of the excitatory postsynaptic current (e.p.s.c.) in response to the drug without any apparent changes in the resting membrane current. These data suggest that haloperidol and loxapine may act by enhancing excitatory synaptic transmission in some areas of the brain, and that novel antipsychotic clozapine differs in its mechanism of action.