Effects of chronic haloperidol on reaction time and errors in a sustained attention task: partial reversal by anticholinergics and by amphetamine.
The attentional and motor-disruptive effects of low doses of haloperidol were studied in a sustained attention task performed by rats. Five separate groups (n = 7 or 8) of rats were trained to react to a 0.125-sec visual stimulus by executing a nose-poke response within 3 sec of stimulus presentation. Each group of rats received its own dose (0.0, 0.02, 0.04, 0.08 or 0.12 mg/kg) of haloperidol daily for 3 months, and from the 1st week onward dose-effects on reaction time were quite stable across time. Haloperidol treatment disrupted the sustained attention task performance by decreasing the number of behavior-initiated stimulus presentations, decreasing the number of reinforcers earned, increasing the proportion of errors of omission and increasing reaction time to the target stimulus. Testing of challenge drugs began after 23 days of haloperidol treatment. Scopolamine (0.1 and 0.2 mg/kg), benztropine (1.0, 3.0 and 6.0 mg/kg) and d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) ameliorated haloperidol-induced reaction time slowing, whereas only benztropine and amphetamine lessened haloperidol-induced errors of omission. The 2.0-mg/kg dose of amphetamine by itself produced a significant increase in errors of omission without affecting reaction time. Haloperidol effectively normalized this amphetamine-induced disruption in attention. The results are consistent with a dopaminergic involvement in the expression of both attention and motor processes.
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, New York, USA.
B J
BJ
Brockel
S C
SC
Fowler
D018663:Adrenergic Agents / Q000494:pharmacology; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001590:Benztropine / Q000008:administration & dosage / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D006220:Haloperidol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology
D018663:Adrenergic Agents; D018680:Cholinergic Antagonists; D018492:Dopamine Antagonists; D004338:Drug Combinations; D001590:Benztropine; D000661:Amphetamine; D012601:Scopolamine; D006220:Haloperidol