There is increasing experimental evidence of a neuroprotective effect of cannabinoids in experimental models including ischemia (Nagayama et al. 1999; Braida et al. 2000, 2003; van der Stelt et al., 2001a, 2001b; Veldhuis et al., 2003; Marsicano et al., 2003) and head trauma (Panikashvli et al., 2001). D9-THC, the major and psychoactive constituent of marijuana, is known to exert protective actions either in vitro, in rat cortical neurons (Hampson et al., 1998), or in vivo, in a model of rat forebrain ischemia (Louw et al., 2000) and neurotoxicity (van der Stelt et al., 2001; El-Remessy et al., 2003). However the role of CB1 cannabinoid receptor on D9-THC -induced neuroprotection is still controversial since partial (El-Remessy et al., 2003) or any (Hampson et al., 1998; van der Stelt et al., 2001) antagonism was found. The aim of the present work was to further investigate in vivo the effect of post-ischemic treatment with D9-THC on transient global cerebral ischemia in gerbils using a wide range of doses (0.05 – 2 mg/kg) and to evaluate the role of CB1 cannabinoid receptor using the selective CB1 cannabinoid antagonist SR 141716. Gerbils, previously submitted to bilateral carotid occlusion for 10 min, were treated with D9-THC 5 min after recirculation and monitored for 7 days. Electroencephalographic (EEG) mean total spectral power (on Day 7), spontaneous motor activity (on Day 1) and cognitive function (on Day 3), were evaluated as parameters known to be hardly influenced by cerebral ischemia. D9-THC protected against ischemia-induced EEG flattening and hyperlocomotion, evaluated in an activity cage, with a dose-dependent bell-shaped curve, the maximal active dose being 1 mg/kg. Ischemia-induced memory impairment, evaluated through the passive avoidance test was blocked by D9-THC from 0.5 to 2 mg/kg. Preliminary results indicate that the neuroprotection by D9-THC is in part mediated by the cannabinoid receptor CB1.
Neuroprotection induced by delta-9-THC in a model of transient global cerebral ischemia / Simona Pegorini, Daniela Braida, Chiara Verzoni, Chiara Guerini Rocco, Mariaelvina Sala. ((Intervento presentato al 2. convegno European Workshop on Cannabinoid Research tenutosi a Busto Arsizio nel 29-30 Aprile 2005.
|Titolo:||Neuroprotection induced by delta-9-THC in a model of transient global cerebral ischemia|
|Data di pubblicazione:||29-apr-2005|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||Neuroprotection induced by delta-9-THC in a model of transient global cerebral ischemia / Simona Pegorini, Daniela Braida, Chiara Verzoni, Chiara Guerini Rocco, Mariaelvina Sala. ((Intervento presentato al 2. convegno European Workshop on Cannabinoid Research tenutosi a Busto Arsizio nel 29-30 Aprile 2005.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|