Infusions of scopolamine in dorsal hippocampus reduce anticipatory responding in an appetitive trace conditioning procedure

Abstract

Introduction: Trace conditioning is impaired by lesions to dorsal hippocampus, as well as by treatment with the muscarinic acetylcholine antagonist scopolamine. However, the role of muscarinic receptors within hippocampus has received little attention.

Methods: The present study examined the effects of intra-hippocampal infusion of scopolamine (30 µg/side) in an appetitive (2 vs. 10 s) trace conditioning procedure using sucrose pellets as the unconditioned stimulus (US). Locomotor activity (LMA) was examined in a different apparatus.

Results: Intra-hippocampal scopolamine reduced responding to the 2 s trace conditioned stimulus (CS). Intra-hippocampal scopolamine similarly depressed responding within the inter-stimulus interval (ISI) at both 2 and 10 s trace intervals, but there was no such effect in the inter-trial interval. There was also some overall reduction in responding when the US was delivered; significant at the 10 s but not at the 2 s trace interval. A similar pattern of results to that seen in response to the CS during acquisition was shown drug-free (in the 5 s post-CS) in the extinction tests of conditioned responding. LMA was increased under scopolamine.

Conclusions: The results suggest that nonspecific changes in activity or motivation to respond for the US cannot explain the reduction in trace conditioning as measured by reduced CS responding and in the ISI. Rather, the findings of the present study point to the importance of associative aspects of the task in determining its sensitivity to the effects of scopolamine, suggesting that muscarinic receptors in the hippocampus are important modulators of short-term working memory.

Keywords: dorsal hippocampus; rat; scopolamine; trace conditioning.

Figure 1

(a) Photograph of a representative placement which illustrates the area around the injection which is also representative of the degree of gliosis seen as a result of the microinfusions. (b) Approximate locations of infusion cannula tips, in the dorsal hippocampus. Placements are shown on coronal plates adapted from Paxinos and Watson (1998), with numbers indicating distance from bregma in millimeters

Figure 2

Mean nose‐pokes are shown as a function of the 4 days of conditioning (D1 to D4) for (a) the 5 s of the inter‐trial interval (ITI) just prior to conditioned stimulus (CS) presentation (pre‐CS) as compared to those (b) during the 5 s CS presentation or (c) in the 5 s when food was delivered (US). Diamonds denote rats conditioned at the 10 s trace interval, and circles denote rats conditioned at the 2 s trace interval after bilateral scopolamine infusion (30 µg in 0.5 µl/side) in dorsal hippocampus (black fill). White fill denotes control groups of rats conditioned after microinfusion of saline vehicle. N = 9–10 rats per group. Error bars represent the standard error of the mean

Figure 3

Mean total nose‐pokes are shown as a function of the 4 days of conditioning (a) during the 2 s inter‐stimulus interval and (b) during the 10 s inter‐stimulus interval. Gray circles denote rats conditioned after bilateral microinfusion into dorsal hippocampus of scopolamine at (30 µg in 0.5 µl/side) or saline vehicle. White circles denote rats conditioned after microinfusion of saline vehicle. N = 9–10 rats per group. Error bars represent the standard error of the mean

Figure 4

Effect of microinfusion of scopolamine on spontaneous activity. Rats were habituated to the activity chambers for 30 min before bilateral microinfusion of scopolamine at 30 µg in 0.5 µl/side (gray circles) or saline vehicle (white circles). Locomotor activity was then monitored for an additional 60 min. N = 12 rats per group. Error bars represent the standard error of the mean