Adult mice were administered either the
noradrenaline (NA)
neurotoxin,
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (
DSP4) or distilled water (control), 10-12 days before motor activity testing, and 6 h before testing all the mice were administered
reserpine (10 mg/kg), the monoamine-depleting agent. The interactive effects of (I)
clonidine, the alpha(2)-adrenoceptor agonist, with the
dopamine (DA) agonist,
apomorphine, and the alpha(2)-antagonist,
yohimbine, and (II) with either
yohimbine or the alpha(1)-antagonist,
prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that
apomorphine (3 mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the
DSP4 mice. Co-administration of
clonidine (3 mg/kg) with
apomorphine potentiated the effects of
apomorphine on motor activity and this effect was enhanced markedly by
DSP4 pretreatment.
Yohimbine (10 mg/kg) antagonized the motor activity-stimulating effects of
apomorphine in both DSP4-treated and control mice. Co-administration of
clonidine with
apomorphine, following
yohimbine, restored motor activity levels to those obtained in the absence of
yohimbine and this effect upon locomotor activity was enhanced by
DSP4 pretreatment. The effects of
clonidine on motor activity were enhanced by NA-
denervation. Prazzosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-min period but was not affected by
DSP4 treatment. Analysis of post-
decapitation convulsions (PDCs) indicated loss of the reflex by
DSP4 pretreatment.
Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to
neurologic disorders such as
parkinsonism.