Showing papers by "Francesco E. Pontieri published in 1993"

Treatment with cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord.

Abstract: The abortive axonal regeneration in the central nervous system (CNS) of mammals has been attributed to a series of inhibitory factors. Previous reports suggest the development of autoimmune reactions following CNS lesion in mammals. In this study we investigated whether immunosuppressive treatment with cyclosporine A is able to facilitate axonal regeneration in rats submitted to complete transverse section of the spinal cord at the level of T7-T8. Treated animals received daily subcutaneous injections of cyclosporine A (2.5 mg/kg), while control rats were given a similar treatment with saline. Immunosuppression was begun immediately after spinal cord transection. Strong evidence of morphological axonal regeneration was observed 15 days after surgery in all cyclosporine A treated animals. Furthermore, treatment with cyclosporine A markedly reduced the seric immune reaction elicited by the lesion. The results of this study, although preliminary, provide further evidence for the development of autoimmune processes following lesion in the CNS, and suggest that blocking of the immune reaction facilitates axonal regeneration in the rat.

Local cerebral glucose utilization after D1 receptor stimulation in 6-OHDA lesioned rats: effect of sensitization (priming) with a dopaminergic agonist.

Abstract: In rats bearing unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopaminergic nigro-striatal neurons, a single administration of a D-2 agonist (LY 17155) potentiates the contralateral turning induced by a D-1 agonist (SKF 38393). To identify the neural substrate of this form of sensitization (priming), we studied the local cerebral glucose utilization (lCMRglc) in 6-OHDA lesioned animals treated, 3 days apart, as follows: (1) saline-saline, (2) LY 171555-saline, (3) saline-SKF 38393 and (4) LY 171555-SKF 38393. The unilateral 6-OHDA lesion per se (Sal-Sal) produced increases in lCMRglc in the globus pallidus (GP) and in the lateral habenula (LH) of the lesioned hemisphere. lCMRglc in LY-Sal group were similar to those measured in the Sal-Sal group. Administration of SKF 38393 to drug-naive rats (Sal-SKF) abolished the lesion-induced metabolic asymmetry in the LH but did not have any effect on the GP; furthermore, it increased lCMRglc in the substantia nigra pars reticulata (SNr) of the lesioned side. After priming with LY 171555, administration of SKF 38393 (LY-SKF) produced marked metabolic asymmetries by increasing lCMRglc in the SNr and entopeduncular nucleus (EP), and decreasing it in the LH of the lesioned side. These changes were also significant when compared to the corresponding values of the other experimental groups. Again, in LY-SKF group no modification of the lesion-induced metabolic asymmetry in the GP was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic mapping of the pharmacological and toxicological effects of dopaminergic drugs in experimental animals.

Abstract: Functional consequences of pharmacological and toxicological manipulations of the dopaminergic systems were evaluated by means of the 2-[14C]deoxyglucose (DG) method for measuring local rates of cerebral glucose utilization. Administration of dopamine agonist drugs modifies glucose metabolism in selected brain areas. Several factors, such as the compound used, the dose, length, and modality of the treatment, and the interval of time between the end of the treatment and the measurement of glucose utilization, contribute to define the topography and intensity of the changes. The differences refer to distinct activation of subtypes of dopamine receptors, to secondary involvement of other neurotransmitter receptor systems, and to modification of the receptor sensitivity occurring during the treatment. Other variables that interfere with the motivated behavior induced by psychostimulants may also affect the metabolic pattern. A few changes in glucose utilization are, however, common to most dopamine agonist drugs. High doses, which induce stereotypic behavior, produce metabolic changes in the extrapyramidal system. Low doses of psychostimulants, which elicit locomotion and exploratory behavior and produce reinforcement, increase glucose metabolism in the limbic system, particularly in the nucleus accumbens. Metabolic mapping in monkeys bearing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesions of the dopaminergic areas in the brainstem contributed to define the key role of the striatopallidal pathway in the production and maintenance of the motor abnormalities that characterize parkinsonism. Metabolic patterns associated with unilateral 6-hydroxydopamine lesion of the nigrostriatal neurons in the rat are modified by dopamine agonist drugs. Specific changes are produced by selective D1 or D2 agonists. In rats bearing unilateral 6-hydroxydopamine lesion, the DG method also revealed functional effects produced by the interaction between D1 and N-methyl-D-aspartate receptors.