On the role of ascending catecholaminergic projections in intracranial self-stimulation of the substantia nigra

Abstract

Summary The role of ascending dopaminergic (DA) and noradrenergic (NA) neurons in the rewarding properties of intracranial self-stimulation (ICSS) obtained from electrodes in the zona compacta of the substantia nigra (SNC) was investigated. Rats were trained on a bar-press response to obtain ICSS and then received 6-hydroxydopamine (6-OHDA) lesions of the DA nigrostriatal bundle (NSB) either ipsilateral or contralateral to the electrodes. Lesions ipsilateral to the ICSS electrode, which reduced striatal DA levels to less than 3% of control values, resulted in profound but temporary reductions in ICSS which returned to preoperative levels 8–10 days after the lesions. Identical effects were obtained in animals subjected to NSB lesions contralateral to the electrodes. Alpha-methyl-p-tyrosine at a dose (25 mg/kg) which did not affect responding in unlesioned control animals decreased responding in the ipsilateral and contralateral lesioned groups to a similar extent. The facilitation of responding for ICSS produced by D -amphetamine (1.0 mg/kg) was blocked by the ipsilateral but not by the contralateral NSB lesions. Lesions of ascending NA axons produced by stereotaxic injections of 6-OHDA caudal to the SNC failed to impair ICSS. It is concluded that the deficits in responding for ICSS produced by unilateral 6-OHDA lesions of the NSB can be accounted for in terms of transient motor deficits produced by these lesions. The data indicate that the NSB is not the critical neuronal substrate which mediates the rewarding properties of nigral ICSS. Rather, this system appears to serve a non-essential, modulatory function and is involved in the rate-increasing effects of D -amphetamine on nigral ICSS. No evidence for a role of ascending NA systems in nigral ICSS was obtained.