Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease.

Incidence of severe depression is very common in Parkinson's disease (PD). Use of antidepressants in such cases is known to improve or worsen the existing PD. However, prediction of the effect of antidepressant on symptoms of PD is limited due to lack of suitable animal model. The present study examines the possibility of using haloperidol-induced catalepsy model in rats for this purpose. Antidepressants showed distinct effect on haloperidol-induced catalepsy, although most of them reduced forced-swimming induced immobility. In general, antidepressants with greater noradrenergic reuptake inhibition (desipramine, imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced, whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine) increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant, and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol-induced catalepsy. The results suggest that haloperidol-induced catalepsy model in rats needs to be incorporated in the screening procedure when evaluating the utility of antidepressant drugs for the treatment of depression associated with PD.

Neurobehavioral effects of low level fenvalerate exposure in mice.

Effect of oral administration of fenvalerate, a pyrethroid insecticide was studied in different behavioral paradigms in mice. Fenvalerate at 15, 30 and 45 mg/kg dose increased start latency, decreased ambulation and rearing in open-field, increased immobility in tail-suspension test and attenuated haloperidol-induced catalepsy in a dose-dependent manner. The time-course of data shows that these effects of fenvalerate may sustain up to several hours of its oral administration. The study indicates that pyrethroids can cause adverse behavioral effects even after a very low-level exposure. Although, it is difficult to extrapolate these findings directly to behavioral changes in man, they indicate that subtle behavioral dysfunction also occur in humans at exposures which do not cause acute toxicity.

GABAergic agents modify imipramine analgesia.

The influence of GABA agonists and antagonists on analgesic activity of imipramine (IMA, 20 mg/kg, ip) was studied using the hotplate method. Administration of GABAA receptor agonist muscimol (1 mg/kg, ip), GABAB receptor agonist baclofen (3 mg/kg, ip) or GABA-T inhibitor aminooxyacetic acid (25 mg/kg, ip) increased the analgesic effect of IMA. On the other hand pretreatment of GABAA receptor antagonist bicucukline (2 mg/kg ip), GABAB receptor antagonist delta-amino-n-valeric acid (50 mg/kg, ip) or GABA synthesis inhibitor thiosemicarbazide (50 mg/kg, ip) attenuated the IMA analgesia. These results suggest that the analgesic action of IMA may be mediated by functional alteration of a central GABAergic mechanism and/or subsequent stimulation of GABA receptors.