Progress in neuro-psychopharmacology & biological psychiatry

Behavioral and degeneration changes in the basal forebrain systems of aged rats: a quantitative study in the region of the basal forebrain after levo-acetyl-carnitine treatments assessed by Abercrombie estimation.

PMID 19171177


One group of six male control rats [21 months old] and one group of six male rats of the same age, singularly stored in a cage, and treated with acetyl-l-carnitine-HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial learning/memory Morris maze-water task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 mum thick were cut through the BF regions and processed every 200 mum for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (ANOVA-enzyme: F(1,39)=112.5, P=0.0001; sessions: F(3,39)=10.41, P=0.0001; interaction: F(3,39)=5.09, P=0.0044). Degenerative morphological changes in the BF ChAT-positive cells were observed in the control rats, but not in the treated animals, in: the diagonal band of Broca, the magnocellular preoptic nucleus, the olfactory tubercle, the substantia innominata, and the globus pallidus (ANOVA-enzyme: F(1,2)=14, P=0,0003; structures: F(6,7)=4, P=0,0018; interaction: F(6,7)=3, P=0,0043). In the diagonal band of Broca (P<0.0494) and in the magnocellular preoptic nucleus (P<0.0117) there were significantly fewer ChAT-positive neurons in the aged control rats than in the ALCAR-treated rats. These results demonstrate that in rats aged from 15 to 21 months ALCAR treatment significantly attenuated spatial learning/memory impairment on the Morris maze-water task and also importantly reduced the degeneration in size and number of cholinergic cells in the BF.