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Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a focal form of epilepsy characterized by seizures occurring during non-REM sleep. We have developed and characterized the first mouse model for ADNFLE type III carrying the V287L mutation of the beta2 subunit of neuronal nicotinic receptor. Mice expressing mutant receptors show a spontaneous epileptic phenotype by electroencephalography with very frequent interictal spikes and seizures. Expression of the mutant beta2 subunit is driven by a neuronal-specific tetracycline-controlled promoter, which allows planned silencing of transgene expression in a reversible fashion and tracking the involvement of mutant receptor in crucial phases of epileptogenesis. We found that restricted silencing during development is sufficient to prevent the occurrence of epileptic seizures in adulthood. Our data indicate that mutant nicotinic receptors are responsible for abnormal formation of neuronal circuits and/or long-lasting alteration of network assembly in the developing brain, thus leading to epilepsy.

1 Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils.2 Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg À1 ), given 5 min after recirculation, dose-dependently antagonized the ischemia-induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia.3 Capsaicin, at all tested doses, fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia. 4 Capsaicin dose-dependently antagonized ischemia-induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia. 5 Capsaicin showed a dose-dependent hypothermic effect evaluated for 2 h after recirculation. 6 At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicintreated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg À1 , was obtained. 7 The selective VR1 antagonist, capsazepine (0.01 mg kg À1 ), reversed capsaicin-induced protective effects, in a competitive manner. 8 These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.

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