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Titolo: Cannabinoid CB1 receptors in the paraventricular nucleus and central control of penilemerection: immunohistochemistry,autoradiography and behavvioral studies
Data di pubblicazione: 2007
Abstract: [N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (SR141716A), a selective cannabinoid CB1 receptor antagonist, injected into the paraventricular nucleus of the hypothalamus (PVN) of male rats, induces penile erection. This effect is mediated by the release of glutamic acid, which in turn activates central oxytocinergic neurons mediating penile erection. Double immunofluorescence studies with selective antibodies against CB1 receptors, glutamic acid transporters (vesicular glutamate transporters I and 2 (VGlut1 and VGlut2), glutamic acid decarboxylase-67 (GAD67) and oxytocin itself, have shown that CB1 receptors in the PVN are located mainly in GABAergic terminals and fibers surrounding oxytocinergic cell bodies. As GABAergic synapses in the PVN impinge directly on oxytocinergic neurons or on excitatory glutamatergic synapses, which also impinge on oxytocinergic neurons, these results suggest that the blockade of CB1 receptors decreases GABA release in the PVN, increasing in turn glutamatergic neuro-transmission to activate oxytocinergic neurons mediating penile erection. Autoradiography studies with [H-3](-)-CP 55,940 show that chronic treatment with SIR 141716A for 15 days twice daily (11 mg/kg i.p.) significantly increases the density of CB1 receptors in the PVN. This increase occurs concomitantly with an almost twofold increase in the proerectile effect of SIR 141716A injected into the PVN as compared with control rats. The present findings confirm thatPVN CB1 receptors, localized mainly in GABAergic synapses that control in an inhibitory fashion excitatory synapses, exert an inhibitory control on penile erection, demonstrating for the first time that chronic blockade of CB1 receptors by SIR 141716A increases the density of these receptors in the PVN. This increase is related to an enhanced pro-erectile effect of SIR 141716A, which is still present 3 days after the end of the chronic treatment. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
Tipologia:1.1 Articolo in rivista

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