Presynaptic action of neurotensin on dopamine release through inhibition of D(2) receptor function.

BACKGROUND: Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc). RESULTS: DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D2 autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D2 autoreceptors, quinpirole (1 microM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D2 receptor antagonist, sulpiride (5 microM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8-13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D2 autoreceptors. In addition, initial blockade of D2 autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8-13). CONCLUSION: Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D2 autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.

Complications of Gamma Knife surgery: an early report from 2 Canadian centers.

OBJECT: Gamma Knife surgery (GKS) is used to treat benign and malignant brain tumors, arteriovenous malformations, trigeminal neuralgia, and other conditions. Patients experience reduced neurological morbidity from GKS compared with open microneurosurgery, but risks of radiation injury and technical limitations persist. The authors report treatment complications from the early experience of 2 Canadian GKS programs in Toronto and Sherbrooke. METHODS: In Toronto, a prospective administrative database was searched for adverse events and incomplete treatment administrations. In Sherbrooke, data were acquired by chart review. Patients were accrued until August 1, 2007, and a total of 973 patients were included in this report. RESULTS: During the radiosurgical procedure, 19 patients (2%) suffered anxiety or syncopal episodes, and 2 patients suffered acute coronary events. Treatments were incompletely administered in 12 patients (1.2%). Severe pain was a delayed complication: 8 patients suffered unexpected headaches, and 9 patients developed severe facial pain. New motor deficits developed in 11 patients, including edema-induced ataxia in 4 and one case of facial weakness after treatment of a vestibular schwannoma. Four patients required shunt placement for symptomatic hydrocephalus, and 16 patients suffered delayed seizures. CONCLUSIONS: Gamma Knife surgery is a minimally invasive treatment modality for many intracranial diseases. Treatment is not risk free, and some patients will develop complications; these are likely to decrease as institutional experience matures. Expanding availability and indications necessitate discussion of these risks with patients considering treatment.