Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization

This study assessed behavioural and neurochemical effects of i.c.v. injecti ons of both the cholinergic toxin 192 IgG-saporin (2 mu g) and the serotone rgic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 mu g) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-ma ze alternation, beam walking, Morris water-maze (working and reference memo ry) and radial-maze performances, After killing by microwave irradiation, t he concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic ac id (5-HIAA) were measured in the hippocampus, frontoparietal cortex and str iatum. 192 IgG-saporin reduced the concentration of acetylcholine by simila r to 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum, 5,7-DHT lesions reduced the concentration of serotonin by 60 % in the frontoparietal cortex and 80% in the hippocampus and striatum. Nor adrenaline was unchanged in all structures except the ventral hippocampus w here it was slightly increased in rats given 192 IgG-saporin, Cholinergic l esions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effec t, Rats with combined lesions were more active than those with only seroton ergic lesions, showed motor dysfunctions similar to those found in rats wit h cholinergic lesions alone, and exhibited impaired performances in the T-m aze alternation test, the water-maze working memory test and the radial-maz e, Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selec tively damage cholinergic and serotonergic neurons, and confirm that cholin ergic-serotonergic interactions play an important role in some aspects of m emory, particularly in spatial working memory.