The effect of nonspatial water maze pretraining in rats subjected to serotonin depletion and muscarinic receptor antagonism: a detailed behavioural assessment of spatial performance

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

“…The latter point is important given that the water maze task is highly stressful, as documented by a rapid and large surge in serum corticosterone early in training (Beiko et al, 1997b). The use of pretraining together with a detailed behavioral analysis has shown that strategy impairments and sensorimotor disturbances, but not spatial learning impairments, are the main cause of increased search times in naive animals given SCO (Beiko et al, 1997a;Cain et al, 2000;Saucier et al, 1996), or the benzodiazepine diazepam (Cain, 1997;Cain et al, 2000), or any of a variety of NMDA receptor antagonists (Bannerman et al, 1995;Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Hoh et al, 1999;Saucier and Cain, 1995). In each of the above studies pretrained drugged rats were indistinguishable from controls on behavioral measures of spatial learning.…”

“…This was performed because swimming away from the wall to search the inner region of the pool is an essential strategy in this task, and has a major impact on the search time measure of acquisition (Morris, 1989;Schenk and Morris, 1985). Various pharmacological treatments and brain lesions markedly impair acquisition of this strategy by naive rats (Beiko et al, 1997a;Cain, 1998;Cain et al, 1996).…”

“…Thus rats given a low dose of either PRO or scopolamine (SCO), a muscarinic cholinergic antagonist, had search times comparable to saline controls, whereas a combination of the two treatments significantly increased search times (Decker et al, 1990). Similarly, rats given PCPA had no water maze impairment, and rats given only SCO had a moderate impairment, whereas rats given both treatments were severely impaired (Beiko et al, 1997a). The findings from these experiments are important because they reveal a greater than additive impairing effect on behavior compared to the effect of each drug alone.…”

“…These include treatments that antagonize muscarinic, NMDA, or AMPA receptors or that serve as GABA agonists by binding to the benzodiazepine receptor (Bannerman et al, 1995;Beiko et al, 1997a;Cain, 1997Cain, , 1998Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Morris et al, 1986;Morris, 1989;Saucier and Cain, 1995;Saucier et al, 1996;Vanderwolf, 1987;Whishaw, 1989;Whishaw and Tomie, 1987). Certain other treatments, such as depletion of serotonin by p-chlorophenylalanine (PCPA), antagonism of b-adrenergic receptors with propranolol (PRO), or destruction of noradrenalin-containing neurons in the locus coeruleus, have little effect or no on water maze performance (Beiko et al, 1997a;Decker et al, 1990;Vanderwolf and Baker, 1996). In contrast to treatment with a single drug, combined treatment with two drugs can markedly impair water maze performance even if treatment with either drug alone causes little or no impairment.…”

“…Studies indicate that in many cases drug treatments impair acquisition and use of required water maze strategies by naive rats (Bannerman et al, 1995;Beiko et al, 1997a;Cain, 1997Cain, , 1998Cain et al, 1996Cain et al, , 1997Cain et al, , 2000Saucier et al, 1996), thus obscuring any conclusion on whether the drug specifically impairs spatial learning. This problem could be avoided if the strategy learning and spatial learning components of the task could be separated.…”