Combined beta-adrenergic and cholinergic antagonism produces behavioral and cognitive impairments in the water maze: implications for Alzheimer disease and pharmacotherapy with beta-adrenergic antagonists.
This study examined the effects of beta-adrenergic and muscarinic blockade on spatial learning and strategy use in the water maze. Male Long-Evans rats received systemic injections of propranolol (PRO; 10 or 20 mg/kg) or scopolamine (SCO; 0.3 or 1.0 mg/kg) either singly or in combination. To separate strategies learning from spatial learning approximately half of the rats underwent water maze strategies pretraining prior to drug administration and spatial training. PRO did not impair performance in any group. SCO impaired naive but not pretrained rats. PRO and SCO given together in high doses impaired all aspects of behavior in both naive and pretrained rats, and caused sensorimotor disturbances in some groups. PRO (10 mg/kg) and SCO (0.3 mg/kg) together caused a specific spatial reversal learning impairment in pretrained rats without causing strategies impairments or sensorimotor disturbances. Nadolol administered with SCO failed to produce the same impairments as PRO, suggesting that PRO produced its effects by acting on central nervous system sites. These results point to a greater than additive impairing effect of PRO and SCO on adaptive behavior, and a specific role for beta-adrenergic and cholinergic systems working in conjunction in spatial learning. They also suggest that some of the behavioral and cognitive impairments seen in Alzheimer patients or patients receiving pharmacotherapy with beta-adrenergic antagonists in which cholinergic activity is also compromised may result from the combined impairment of beta-adrenergic and cholinergic systems.
Saber
Andrea J
AJ
Department of Psychology, Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada.
Cain
Donald P
DP
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000009:adverse effects; D009248:Nadolol / Q000009:adverse effects; D011433:Propranolol / Q000009:adverse effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012601:Scopolamine / Q000009:adverse effects*; D013037:Spatial Behavior / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D009248:Nadolol; D011433:Propranolol; D012601:Scopolamine