In vivo brain incorporation of [1-14C]arachidonate in awake rats, with or without cholinergic stimulation, following unilateral lesioning of nucleus basalis magnocellularis.

Regional brain incorporation of a radiolabeled unsaturated fatty acid, [1-14C]arachidonic acid (14C-AA), was measured in awake rats following unilateral lesioning of the nucleus basalis magnocellularis (NBM). Right-sided lesions were produced in 3-month-old, male rats by stereotaxic injection of 10 micrograms ibotenic acid. Two weeks after lesioning, rats were subjected to one of two protocols: (1) 5 min intravenous infusion of 14C-AA (170 microCi/kg); or (2) i.p. injection of arecoline (5 mg/kg), a cholinergic agonist, followed by 5 min intravenous infusion of 14C-AA. All animals were killed 15 min postinfusion. Brains were frozen and sectioned for quantitative autoradiography or were stained for acetylcholinesterase (AChE). Animals with unilateral NBM lesions displayed reduced AChE staining in prefrontal, frontal and parietal cortices of the lesioned side, but there was no right-left difference in incorporation of 14C-AA without cholinergic stimulation. Arecoline administration increased 14C-AA incorporation into the prefrontal and frontal cortices ipsilateral to the NBM lesion as compared to the contralateral side and the increase was most prominent in deeper cortical layers such as layers IV and V. Right-left differences in incorporation were not apparent in parietal, temporal, or occipital cortices, where reduction of AChE activity was minimal or absent, nor in subcortical structures. The results suggest that the intravenous 14C-AA technique combined with cholinergic stimulation can be used to detect compensatory regulation of phospholipid-coupled signal transduction caused by a deficit in cholinergic input into the cerebral cortex.