Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl.
Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n=10), non-helpless (cNLH, n=12) and wild type (WT, n=8) Sprague Dawley rats. The animals were exposed to an open field for 10min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs on the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n=4-5 per group), chronic treatment with a high dose of the monoamine oxidase (MAO)-B inhibitor deprenyl (10mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning.
Schulz
Daniela
D
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, United States. dschulz@bnl.gov
Mirrione
Martine M
MM
Henn
Fritz A
FA
D000375:Aging; D000818:Animals; D001007:Anxiety / Q000178:diet therapy / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology*; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology; D006380:Helplessness, Learned; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D013045:Species Specificity; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline