ABSTRACT
OBJECTIVE: The aim of this study was to test the hypothesis that synthesis of nitric oxide (NO) and activation of CB1 receptors have opposite effects in a behavioural animal model of panic and anxiety. METHODS: To test the hypothesis, male Wistar rats were exposed to the elevated T-maze (ETM) model under the following treatments: L-Arginine (L-Arg) was administered before treatment with WIN55,212-2, a CB1 receptor agonist; AM251, a CB1 antagonist, was administered before treatment with L-Arg. All treatments were by intraperitoneal route. RESULTS: The CB1 receptor agonist, WIN55,212-2 (1 mg/kg), induced an anxiolytic-like effect, which was prevented by pretreatment with an ineffective dose of L-Arg (1 mg/kg). Administration of AM251 (1 mg/kg), a CB1 antagonist before treatment with L-Arg (1 mg/kg) did not produce anxiogenic-like responses. CONCLUSION: Altogether, this study suggests that the anxiolytic-like effect of cannabinoids may occur through modulation of NO signalling.
Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety/drug therapy , Behavior, Animal/drug effects , Endocannabinoids/antagonists & inhibitors , Panic/drug effects , Animals , Disease Models, Animal , Locomotion/drug effects , Male , Maze Learning/drug effects , Nitric Oxide , Piperidines , Pyrazoles , Rats , Rats, Wistar , Receptor, Cannabinoid, CB1/antagonists & inhibitorsABSTRACT
The dorsolateral periaqueductal grey (dlPAG) is proposed to play a role in the elaboration of defensive behaviors. Nitric oxide (NO) donors, injected into this region, induce flight reactions. The reactions have also been observed after electrical or chemical stimulation of the inferior colliculus (IC). The enzyme responsible for NO formation, neuronal nitric oxide synthase (nNOS), is expressed in the IC. The aims of this study were to investigate if NO donors injected into the IC would also cause aversive reactions and if these reactions would involve activation of NMDA receptors. The results showed that 3-morpholinosylnomine hydrochloride (SIN-1; 300 nmol), an NO donor, injected into the central nucleus but not into the dorsal cortex of the IC (CIC and DCIC, respectively) of male Wistar rats induced flight reactions characterized by galloping and jumps. Pretreatment (10 min) with methylene blue (MB; 100 or 200 nmol), a guanylate cyclase (GC) inhibitor, partially inhibited this flight reaction, decreasing the number of jumps. 8-Bromo-cGMP (8-Br-GMP), a membrane-permeable cGMP analogue, increased the number of contralateral turnings. Pretreatment (10 min) with the NMDA receptor antagonist amino-7-phosphonoheptanoic acid (AP7; 2 nmol) completely prevented the effects of SIN-1. It is concluded that NO may induce aversive reactions in the CIC and that these reactions depend on NMDA receptor activation. They may also partially involve facilitation of GC activity.
