Neonatal cholinergic lesions and development of exploration upon administration of the GABAa receptor agonist muscimol in preweaning rats.

ABSTRACT

Neonatal rats were administered 192 IgG-saporin (192 IgG-Sap), a selective cholinergic immunotoxin, on postnatal day (PND) 7. Behavioural responsiveness to muscimol, a GABAa receptor agonist, was then assessed using locomotor activity and object exploration tests on PND 18. In Experiment 1, 192 IgG-Sap-lesioned and control rats were injected with the GABAa agonist, muscimol, on PND 18 and tested in a standard open field test. Muscimol reduced rearing responses in both control and 192 IgG-Sap-lesioned animals whereas reduced wall-rearing responses occurred in control animals only. 192 IgG-Sap also reduced rearing and wall-rearing responses. In Experiment 2, muscimol effects were evaluated on PND 18 in a spatial open field test in which object exploration in addition to locomotion and rearing responses was assessed. Neonatal cholinergic lesion per se increased locomotion during object exploration while decreasing time spent exploring objects. Depressant effects of muscimol on object exploration were also evident. As a whole, these data provide evidence for (i) basal forebrain (BF) cholinergic control on locomotor activity and object exploration and (ii) GABAa-mediated regulation of selective behavioural patterns associated with locomotion and exploration in weaning rats. Neonatal cholinergic lesions, however, do not appear to alter reactivity to GABAergic agonists in juvenile rats.