Modulation of anxiety by acute blockade and genetic deletion of the CB1 cannabinoid receptor in mice together with biogenic amine changes in the forebrain

The antinociceptive effect of acetylsalicylic acid is differently affected by a CB1 agonist or antagonist and involves the serotonergic system in rats

“…SR141716A failed to modify 5-HT levels and did not influence HU210 plus ASA or ASA serotonergic activity; this is probably due to the lack of modification in 5-HT levels, a change which occurs only at doses higher than 3 mg/kg (Tzavara et al 2003;Thiemann et al 2009). Thus, our findings regarding SR141716A indirectly support the hypothesis that the activity of ASA, alone or in combination, occurs only when the central serotonergic system is involved.…”

“…The used dosage was proved not to elicit centrallymediated adverse side effects, i.e. increased anxiety after 3 mg/kg of SR141716A (Thiemann et al 2009), which could confound pain threshold measurements.…”

Alterations in Corticolimbic Dendritic Morphology and Emotional Behavior in Cannabinoid CB1 Receptor-Deficient Mice Parallel the Effects of Chronic Stress

“…The role of this system is highlighted by findings that pharmacological or genetic disruption of endocannabinoid signaling produces a phenotypic state which is strikingly reminiscent of changes that are evoked by exposure to chronic stress, such as increased emotionality (Haller et al 2002;Martin et al 2002;Rodgers et al 2005;Patel and Hillard 2006;Aso et al 2008;Thiemann et al 2009;Beyer et al 2010), exaggerated stress responses Patel et al 2004;Steiner, Marsicano, Nestler, et al 2008), and reductions in hippocampal plasticity and cellular resilience (Jin et al 2004;Aguado et al 2005; Kim et al 2006; Lee et al 2009;Beyer et al 2010). Furthermore, reduced levels of circulating endocannabinoids have been documented in individuals diagnosed with major depression (Hill, Miller, et al 2008;, and the widespread use in humans of a CB 1 receptor antagonist revealed that blockade of endocannabinoid signaling increased indices of anxiety and depression in a subset of individuals with no history of mental illness (Christensen et al 2007;Nissen et al 2008;Moreira et al 2009).…”

Endocannabinoids and Mental Disorders

“…CB1r blockade, through systemic SR141716, AM251, and AM281 administration, has been found to exert anxiogenic-like effects in several preclinical models (Arevalo et al 2001;Dono and Currie 2012;Dubreucq et al 2012;GambleGeorge et al 2013;Haller et al 2004;Kamprath et al 2006Kamprath et al , 2009Lin et al 2011;Litvin et al 2013;Navarro et al 1997;O'Brien et al 2013;Patel and Hillard 2006;Plendl and Wotjak 2010;Rodgers et al 2005;Sink et al 2010a, b;Thiemann et al 2009;Varga et al 2012). In contrast, a few other studies have demonstrated either no effect (Bortolato et al 2006;Kathuria et al 2003) or an anxiolytic-like activity of CB1r antagonists (Akinshola et al 1999;Degroot and Nomikos 2004;Griebel et al 2005;Haller et al 2002;Rodgers et al 2003;Rubio et al 2008).…”