A RAT MODEL OF DISTRACTIBILITY - EFFECTS OF DRUGS MODIFYING DOPAMINERGIC, NORADRENERGIC AND GABAERGIC NEUROTRANSMISSION

A procedure for analyzing effects of drugs on distractibility is propo sed. Rats are trained to traverse a straight runway with a sucrose sol ution as reinforcement. Once the response has been acquired, an additi onal runway ending in an empty box is connected. The time spent invest igating this additional runway is the measure of distractibility. Amph etamine, 1 mg/kg i.p., increased distractibility. In rats that were ne ver reinforced, amphetamine at a dose of 1 mg/kg reduced the time spen t in the additional runway. This shows that the effects of amphetamine in the reinforced animals cannot be interpreted as enhanced explorati on. Furthermore, the benzodiazepines diazepam (2 and 4 mg/kg, i.p.) an d chlordiazepoxide (2.5, 5 and 10 mg/kg, i.p.), known to enhance explo ration of novel environments, did not affect the time spent in the add itional runway in sucrose-reinforced animals. It was concluded that th e procedure indeed is a model of distractibility. The dopamine antagon ist cis(Z)-flupenthixol, at a dose of 0.25 mg/kg, i.p.? blocked the ef fects of amphetamine, 1 mg/kg. Flupenthixol itself, in doses of 0.25 a nd 0.5 mg/kg, did not affect the time spent in the additional runway. This suggests that enhanced dopaminergic activity indeed is responsibl e for the effects. This proposal is further supported by experiments s howing that the noradrenaline precursor dihydroxyphenylserine (10mg/kg + carbidopa, 50 mg/kg, both i.p.) and the noradrenergic neurotoxin DS P4 (50 mg/kg, i.p.) had no effect on distractibility. Moreover, amfone lic acid, a dopamine releaser with slight or no effect on noradrenergi c neurotransmission, had effects very similar to those of amphetamine when given in doses of 0.25 and 0.5 mg/kg, i.p. A lower dose, 0.125 mg /kg, was ineffective. Taken together, these data suggest that enhanced dopaminergic neurotransmission increases distractibility in the rat. However, both amphetamine and amfonelic acid may stimulate serotonin r elease. Until serotonergic drugs have been tested, a contribution of t his transmitter cannot be ruled out. The distraction procedure may con stitute an animal model of some kinds of disordered information proces sing.