Short and long term plasticity after lesioning of the cell body or terminal field area of the dopaminergic mesocorticolimbic system in the rat

To investigate within one study regenerative capacities of dopaminergic axo ns and cell bodies, short and long term recovery of behavioral and biochemi cal impairments following a bilateral 6-hydroxydopamine (6-OHDA) lesion of the ventral tegmental area (VTA)-nucleus accumbens (NAc) pathway was invest igated in rats. Novelty-induced motility, presynaptic functions and the lev els of dopamine (DA) and its metabolites were reduced when cell bodies in t he VTA or axons in the NAc were lesioned. Spontaneous recovery of the behav ioral deficit was observed 4 weeks after a lesion of the NAc. Subsequently presynaptic functions recovered as shown by the reappearance of low dose ap omorphine (50 mg/kg)-induced hypomotility, normalization of [H-3]dopamine u ptake, reinnervation of the NAc and normalization of levels of DA and its m etabolites within 24 weeks. In contrast, after a VTA lesion no recovery was observed during 48 weeks, neither from hypomotility and loss of the low do se apomorphine response nor from decreased [H-3]dopamine uptake and levels of DA in the NAc. Short term postsynaptic supersensitivity (hypermotility u pon a higher dose of apomorphine (125 mg/kg)) was present 1 and 4 weeks aft er the lesion but not thereafter. A near total absence of dopaminergic neur ons in the VTA and axone in the NAc were found 24 weeks postlesion. Treatme nt with the ACTH-(4-9) analog ORG 2766 (10 mg/kg s.c., 6 days once daily) f acilitated recurrence of presynaptic functions after a lesion of axons but had no short or long term effect when cell bodies were lesioned. These find ings substantiate the postulate that the peptide facilitates recovery proce sses. (C) 1999 Elsevier Science B.V. All rights reserved.