Impairments of search behaviour in rats after haloperidol treatment, hippocampal or neocortical damage suggest a mesocorticolimbic role in cognition

Introduction: In view of reports that fimbria-fornix or hippocampal lesions impair working rather than reference memory in a radial maze (Olton et al., 1979) the performance of rodents with hippocampal damage was examined on a hole-board search task. Methods: Food-deprived animals searched for food pellets placed consistently in 4 holes of a 16-hole-board (figure 1). They were presented with 11 sessions of 10 trials/session. There were three groups of animals, - one with aspiration lesions of the hippocampus and overlying neocortex, one with damage only to the overlying neocortex and sham-controls that went through the procedure but the brain was left intact (Oades and Isaacson, 1978). Half of each group received haloperidol (0.275 mg/kg) or saline injections 15 minutes before each of the sessions 4-10. Working memory error = a visit to a correct hole that has just been visited, and thus no longer contains a food pellet. Reference memory error = visit to a hole that is never baited. Results: 1/ Hippocampal damage resulted in poorer performance on both working and reference memory measures: this was unaffected by haloperidol treatment. 2/ Neuroleptic treatment also impaired the performance of the sham-controls on both measures. 3/ Animals with neocortical damage were impaired on reference mmeory measures alon, after haloperidol treatment. Conclusions: The lack of a neuroleptic effect on performance after hippocampal damage suggests that this lesion does not impair performance on these two measures of memory performance through a dopaminergic mechanism. Haloperidol impaired working memory measures in sham-controls, but only reference memory measures in the neocortical group.. The results imply that there are (at least) three separate mechanisms (i.e. meso-cortico-limbic interactions) at work here involved in shorter- and longer-term consolidation of the consequences of selective attention mechanism required to efficiently learn a search task.


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