We conducted 2 studies to determine the importance of several brain systems for remembering odorants in a go/no-go delayed nonmatching-to-sample (DNMTS) task. In Experiment 1, impairments were observed for lesions of pyriform cortex or (to a lesser extent) the lateral internal medullary lamina of thalamus. Lesions of the entorhinal cortex or the mediodorsal (MDn) or the paracentral and centrolateral (PC-CL) thalamic nuclei did not affect DNMTS. In Experiment 2, an impairment comparable to the pyriform lesion was observed for a lesion of the intralaminar nuclei (PC-CL plus the central medial nucleus) but not for a larger lesion of MDn. None of the lesions in either study affected the ability to learn a 2-choice odor discrimination using go/no-go procedures comparable with the DNMTS task.

The intralaminar thalamic nuclei (ILn) have been implicated as a critical site of pathology in amnesia. Lesions of the ILn have been found to produce behavioral effects comparable to benzodiazepine (BDZ) receptor agonists. We compared the effects of chlordiazepoxide (CDP), a BDZ agonist, and FG 7142, a partial inverse agonist at the BDZ receptor, in rats with thalamic lesions and in unlesioned controls. Delayed matching-to sample (DMS) performances were studied during treatment with ascending doses of CDP, counterbalanced trials with 2.5 mg/kg CDP and saline, ascending doses of FG 7142, and (for unlesioned controls only) counterbalanced trials with saline and higher doses of CDP. CDP had effects similar to the ILn lesion, decreasing response speed and percent correct responding in a delay-independent fashion. These effects were additive with the impairments associated with the ILn lesion. The effects of FG 7142 were more complex. At lower doses, it increased response speed without affecting response accuracy. At higher doses, it diminished both the speed and the accuracy of DMS responding. These results support the hypothesis that ILn lesions and BDZ agonists have similar effects on DMS performance. The biphasic effects observed for FG 7142 are consistent with other evidence that low doses of this drug enhance while higher doses impair memory performance. Although DMS accuracy was not improved, the enhancement observed for response speed provides evidence that partial inverse BDZ agonists have potential utility as treatments for cognitive impairments associated with amnesia.

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