Combined β-Adrenergic and Cholinergic Antagonism Produces Behavioral and Cognitive Impairments in the Water Maze: Implications for Alzheimer Disease and Pharmacotherapy with β-Adrenergic Antagonists

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Abstract
This study examined the effects of β-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 β-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 β-adrenergic antagonists in which cholinergic activity is also compromised may result from the combined impairment of β-adrenergic and cholinergic systems.