Estudo dos efeitos comportamentais do neuropeptídeos em camundongos submetidos a modelos animais de Parkinson

Neuropeptide S (NPS) is the endogenous ligand of a G-protein coupled receptor. Preclinical studies have shown that NPSR receptor activation can promote arousal, anxiolytic-like behavioral, decrease in food intake, besides hyperlocomotion, which is a robust but not well understood phenomenon. Previous findings suggest that dopamine transmission plays a crucial role in NPS hyperactivity. Considering the close relationship between dopamine and Parkinson Disease (PD), and also that NPSR receptors are expressed on dopaminergic nuclei in the brain, the current study attempted to investigate the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of 6-OHDA and systemic administration of haloperidol. Motor deficits induced by 6-OHDA and haloperidol were evaluated on Swiss mice in the rota-rod and catalepsy test. Time on the rotating rod and time spent immobile in the elevated bar were measured respectively in each test. L-Dopa, a classic antiparkinsonian drug, and NPS were administrated in mice submitted to one of the animal models of PD related above. 6-OHDA injection evoked severe motor impairments in rota-rod test, while the cataleptic behavior of 6-OHDA injected mice was largely variable. The administration of L-Dopa (25 mg/kg) and NPS (0,1 and 1 nmol) reversed motor impairments induced by 6-OHDA in the rota-rod. Haloperidolinduced motor deficits on rota-rod and catalepsy tests which were reversed by L-Dopa (100 e 400 mg/kg), but not by NPS (0,1 and 1 nmol) administration. The association of L-Dopa 10 mg/kg and NPS 1 nmol was also unable to counteract haloperidol-induced motor deficits. To summarize, 6-OHDA-, but not haloperidol-, induced motor deficits were reversed by the central administration of NPS. These data suggest that NPS possibly facilitates dopamine release in basal ganglia, what would explain the overcome of motor performance promoted by NPS administration in animals pretreated with 6-OHDA, but not haloperidol. Finally, the presented findings point, for the first time, to the potential of NPSR agonist as an innovative treatment for PD.

O antagonismo do receptor de serotonina do tipo 7 da substância cinzenta periaquedutal dorsal reduz a ansiedade experimental basal, mas não aquela gerada pela retirada do etanol em ratos

Ethanol-dependent individuals who reduce or discontinue its use may present Alcohol Withdrawal Syndrome, which is characterized by unpleasant signs and symptoms, such as anxiety, that may trigger relapses. Ethanol, a psychotropic drug, is able to promote behavioral and neurophysiological changes, acting on different neurotransmitter systems, including the serotonergic, which has also been directly associated with aversive states, including anxiety. This study aimed to investigate the participation of type 7 serotonin receptor (5-HT7) of the dorsal periaqueductal gray (DPAG) on basal experimental anxiety and that caused by ethanol withdrawal. For this, 75-100 days old Wistar rats were subjected to two experiments. On the first one, animals underwent stereotactic surgery for implantation of guide cannulas used for administration of the drug directly into the DPAG. After seven days, the animals received doses of 2.5; 5 and 10 nmols of type 7 receptor antagonist SB269970 (SB) or vehicle intra-DPAG and, ten minutes after, they were exposed to elevated plus maze (EPM). In the following day, the animals were submitted to the same treatment and tested in the open field (OF). In the second experiment, animals received increasing concentrations (2%, 4%, 6%) of ethanol as the only source of liquid diet or water (control group), both with free access to chow. Seventy two hours and ninety six hours after the ethanol withdrawal, animals received SB (2.5 and 5.0 nmols) intraDPAG ten minutes before the test in the LCE and OF, respectively. In experiment 1, the dose of antagonist 10 nmols was able of reversing the anxiety generated by EPM. In the experiment 2, ineffective SB doses on the LCE (2.5 and 5.0 nmol) were not able to reverse the anxiety caused by the ethanol withdrawal in the EPM, although the dose of 2.5 nmols of SB has reversed its hipolocomotor effect in this test. This result suggests that the 5-HT7 receptor is involved in the modulation of the basal experimental anxiety in rats, but not in the anxiety caused by ethanol withdrawal in the DPAG.