A rat model of distractibility: effects of drugs modifying dopaminergic, noradrenergic and GABAergic neurotransmission.
A procedure for analyzing effects of drugs on distractibility is proposed. Rats are trained to traverse a straight runway with a sucrose solution as reinforcement. Once the response has been acquired, an additional runway ending in an empty box is connected. The time spent investigating this additional runway is the measure of distractibility. Amphetamine, 1 mg/kg i.p., increased distractibility. In rats that were never reinforced, amphetamine at a dose of 1 mg/kg reduced the time spent in the additional runway. This shows that the effects of amphetamine in the reinforced animals cannot be interpreted as enhanced exploration. Furthermore, the benzodiazepines diazepam (2 and 4 mg/kg, i.p.) and chlordiazepoxide (2.5, 5 and 10 mg/kg, i.p.), known to enhance exploration of novel environments, did not affect the time spent in the additional runway in sucrose-reinforced animals. It was concluded that the procedure indeed is a model of distractibility. The dopamine antagonist cis(Z)-flupenthixol, at a dose of 0.25 mg/kg, i.p., blocked the effects of amphetamine, 1 mg/kg. Flupenthixol itself, in doses of 0.25 and 0.5 mg/kg, did not affect the time spent in the additional runway. This suggests that enhanced dopaminergic activity indeed is responsible for the effects. This proposal is further supported by experiments showing that the noradrenaline precursor dihydroxyphenylserine (10 mg/kg + carbidopa, 50 mg/kg, both i.p.) and the noradrenergic neurotoxin DSP4 (50 mg/kg, i.p.) had no effect on distractibility. Moreover, amfonelic acid, a dopamine releaser with slight or no effect on noradrenergic 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 release. Until serotonergic drugs have been tested, a contribution of this transmitter cannot be ruled out. The distraction procedure may constitute an animal model of some kinds of disordered information processing.
Agmo
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Escuela de Psicología, Universidad Anáhuac, Mexico City, Mexico.
Belzung
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Rodríguez
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D000446:Aldehyde-Lyases / Q000494:pharmacology; D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001569:Benzodiazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005475:Flupenthixol / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology*; D008297:Male; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018682:GABA Agents; D009287:Naphthyridines; D001569:Benzodiazepines; D009268:Nalidixic Acid; D000661:Amphetamine; C051902:3,4-dihydroxyphenylserine aldolase; D000446:Aldehyde-Lyases; D005475:Flupenthixol; C006486:amfonelic acid; D009638:Norepinephrine