Robert Davis

Continuous low-level apomorphine administration induces motor abnormalities and hallucinogen-like behaviors

Continuous low-level (0.825 mg/kg/h for 20 h) administration of AP through SC in-dwelling silicone reservoirs in the rat induced behavioral and biochemical changes that were similar to those induced by low levels (0.1 mg/kg) of acutely administered AP (decreased behavioral activity and decreased dopamine metabolism in the striatum). With longer periods of continuous AP exposure (40 h or more) the activity-depressing effects of low-level AP diminished. Concurrently a novel behavioral syndrome emerged characterized by limb flicks, body shakes, sudden orienting responses, and motor abnormalities, such as tremors of the jaw muscles, chewing movements, prominent tongue extensions, and body ‘tics’. This behavioral syndrome became more apparent following cessation of drug treatment. These novel behavioral changes, which were accompanied by increased behavioral responsiveness to acutely administered AP and amphetamine, were correlated with increased levels of dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid in the striatum but not the nucleus accumbens. This novel behavioral syndrome appears to reflect a rebound increase in dopaminergic mechanisms in striatum following their chronic suppression by low levels of AP.

Picrotoxin-induced disruption of bidirectional active avoidance behavior and locomotor activity

The effects of picrotoxin (0.75 and 1.5 mg/kg), an antagonist of GABA mediated chloride ion conductance changes, were examined on the acquisition and performance of a bidirectional active avoidance (BAA) response and on locomotor activity. Treatment with this agent disrupted both the acquisition and performance of this task and decreased locomotor activity. This picrotoxin-induced suppression of BAA was reversed by pretreatment with diazepam (2 mg/kg), d-amphetamine (d-AMP, 2.0 mg/kg) and lysergic acid diethylamide (LSD, 10 micrograms/kg) and was reversed partially by cinanserin (5 mg/kg) and methysergide (5 mg/kg). Picrotoxin-induced activity decreases in locomotor activity were antagonized by d-AMP, were partially reversed by LSD but were not reversed by methysergide. It is proposed that picrotoxin disrupts bidirectional active avoidance behavior by increasing the response suppressive effects of aversive stimuli and by inducing a general depression of motility.