Paraventricular hypothalamic CB₁ cannabinoid receptors are involved in the feeding stimulatory effects of Δ⁹-tetrahydrocannabinol

Background/Aims: The paraventricular nucleus of the hypothalamus (PVN) is the target of converging orexigenic and anorexigenic pathways originating from various hypothalamic sites and is, therefore, considered to be the chief site mediating hypothalamic regulation of energy homeostasis. Although a large body of evidence suggests that central CB₁ cannabinoid receptors mediate food intake, it is not clear whether PVN CB₁ receptors are involved in the control of feeding behaviour. The present study therefore examined the effects of intra-PVN administration of Δ⁹-tetrahydrocannabinol (THC) and the cannabinoid receptor antagonist SR 141716 on feeding. Methods: After being habituated to the test environment and injection procedure, sated rats were injected with SR 141716 (0.03-3.0 μg, Experiment 1) alone or in combination with THC (5.0μg, Experiment 2) into the PVN. Food intake and locomotor activity then were recorded for 120 min. Results: Intra-PVN administration of THC produced a significant increases in food intake that was attenuated by SR 141716. Administration of SR 141716 alone did not affect feeding. Locomotor activity was not significantly affected by any drug treatments, suggesting that effects on feeding were not due to a non-specific reduction in motivated behaviour. These findings suggest an important role for PVN cannabinoid signalling in mediating THC-induced feeding behaviour. These results also demonstrate that the blockade of PVN CB₁ receptors alone is insufficient to reduce baseline feeding behaviour under these conditions.