THE EFFECTS OF SCOPOLAMINE, LORAZEPAM, AND GLYCOPYRROLATE ON CLASSICAL-CONDITIONING OF THE HUMAN EYEBLINK RESPONSE

Human eyeblink conditioning, a relatively simple form of learning and memory, has previously been shown to be impaired by the central and pe ripheral anticholinergic scopolamine. The present study compared the b ehavioral effects of scopolamine with the benzodiazepine lorazepam and a peripherally active anticholinergic, glycopyrrolate. Thirty-six hea lthy normal volunteers (mean age: 23.7 years) were studied with 12 ass igned double-blind to each of three drug conditions (0.5 mg scopolamin e IV, 2 mg lorazepam PO, or 0.2 mg glycopyrrolate IV). Subjects underw ent classical conditioning of the eyeblink response in which the condi tioned stimulus was an 80 dB binaural tone, and the unconditioned stim ulus was a 2 psi airpuff to the right eye. Ten trials of unpaired stim ulus presentations were followed by 60 paired trials and finally by an extinction period of five tone-alone presentations. An eyeblink respo nse that occurred during the tone but before the airpuff was scored as a conditioned response (CR), Subjects treated with lorazepam (43% mea n CRs) and scopolamine (51% mean CRs) exhibited a significantly lower asymptotic level of conditioning than those treated with glycopyrrolat e (85% mean CRs; P < 0.01), However, during extinction, lorazepam-trea ted subjects (35% CRs) showed a lower overall level of responding to t he tone than either scopolamine (60% CRs) or glycopyrrolate (62% CRs) treated subjects (P < 0.05). It seems unlikely that these differences could be accounted for by drug-induced alterations in motor responses because there were no significant differences between the three drug c onditions in the frequency,latency, or amplitude of unconditioned resp onses to the airpuff. Overall, our data indicate that scopolamine and lorazepam impair eyeblink conditioning and suggest that some of the ef fects of benzodiazepines and anticholinergics on learning and memory c an be differentiated using this paradigm.