Hippocampal acetylcholine depletion has no effect on anxiety, spatial novelty preference, or differential reward for low rates of responding (DRL) performance in rats

Abstract

We investigated the role of the septo-hippocampal cholinergic projection in anxiety, spatial novelty preference, and differential reward for low rates of responding (DRL) performance. Cholinergic neurons of the rat medial septum (MS) and the vertical limb of the diagonal band of Broca (VDB) were lesioned using the selective immunotoxin, 192 IgG-saporin. Rats were then tested on several behavioral tests previously shown to be sensitive to either (a) hippocampal lesions or (b) nonselective MS/VDB lesions which target both cholinergic and γ-aminobutyric acid (GABA)-ergic projections, or both. Saporin lesions substantially reduced hippocampal cholinergic innervation, resulting in an absence of acetyl cholinesterase staining and markedly reduced choline acetyltransferase activity (mean reduction: 80 ± 5%; range: 50-97%). However, the saporin-lesioned rats did not differ from control rats in any of the behavioral tests. Thus we found no evidence from these lesion studies that the septo-hippocampal cholinergic projection plays an essential role in anxiety, spatial novelty preference, or DRL.

Figure 1

Mean (±standard error of the mean) hippocampal choline acetyltransferase (ChAT) activity in control (CTL) rats (combined unoperated and vehicle-infused) and rats with saporin (SAP) lesions.

Figure 2

Mean (±standard error of the mean) latency to eat on the three food neophobia tests of anxiety for unoperated (un-op), vehicle infused and saporin-lesioned rats. There were no group differences in any of the tests.

Figure 3

Spatial novelty preference. (A) Mean (± standard error of the mean) time spent in the three arms of a y-maze during the test phase of the task. There were no differences between the groups in terms of time spent in the novel or familiar arms. Note that the unoperated (un-op) group spent less time in the start arm than the other two groups, but this was because the un-op group spent more time in the “central area” (i.e., at the choice point). (B) Mean (± standard error of the mean) preference for the novel arm expressed as a ratio (novel/[novel + familiar]). There were no group differences on this measure.

Figure 4

Differential reward for low rates of responding (DRL-15). (A) Mean (±standard error of the mean [SEM]) efficiency in DRL-15 training. Efficiency is computed as [number of rewards/number of lever presses]. Overall, all groups improved their efficiency at the same rate. (B) Interresponse time expressed as frequency of first lever press after reward delivery, in 3-s time bins. The shape of the response curves was equivalent in all three groups. (C) Mean (±SEM) efficiency during the very first block of DRL-15 training. Saporin lesioned rats were significantly less efficient than either the unoperated (un-op) or vehicle controls (* p < .05). (D) Mean (±SEM) efficiency following benzodiazepine (CDP) or saline injections. CDP impaired efficiency in all groups to an equivalent extent.