Scopolamine and pavlovian fear conditioning in rats: Dose-effect analysis

Muscarinic-cholinergic antagonism produces learning and memory deficits in a wide variety of hippocampal-dependent tasks. Hippocampal lesions produce both acquisition deficits and retrograde amnesia of contextual far (fear of the place of conditioning), but do not impact far conditioning to discrete cues (such as a tone). In order to examine the effects of muscarinic antagonism in this paradigm, rate were given 0.01 to 100 mg/kg of scopolamine (or methylscopolamine) either before or after a fear conditioning session in which tones were paired with aversive footshocks. Ear to the context and the tone were assessed by measuring freezing in separate tests. It was found that pretraining, but not post-training, scopolamine severely impaired fear conditioning; methylscopolamine was ineffective in disrupting conditioning. Although contextual far conditioning was more sensitive to cholinergic disruption, high doses of scopolamine also disrupted tone conditioning. Scopolamine did not affect footshock reactivity, but did produce high levels of activity However, hyperactivity was not directly responsible for deficits in conditioning. It was concluded that scopolamine disrupts Cs-US association formation or CS processing, perhaps through an attenuation of hippocampal theta rhythm. [Neuropsychopharmacology 21:731-744, 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.