We have studied the possible modulations by serotoninergic neurotransmission of the effects of the cannabinoid receptor agonist, CP 55,940, on anxiety-related responses in the open field test, a validated behavioural paradigm in rats. Under acute treatment conditions, a low dose of CP 55,940 (10 µg/kg but neither 20 µg/kg nor 40 µg/kg) induced anxiolytic-like effects, whereas high doses (0.2-0.4 and 0.6 mg/kg) of this CB receptor agonist evoked anxiogenic-like responses. The 5-HT1A receptor agonist, ipsapirone (6 mg/kg), when administered alone, induced a marked increase in the number of central squares visited in the open field test, in line with its well established anxiolytic-like properties. Surprisingly, the ipsapirone effect was antagonized by acute as well as subchronic pretreatment with CP 55,940 (0.4 mg/kg/day; 11 days). Acute administration of the 5-HT reuptake inhibitor fluoxetine (3 mg/kg) alone had no observable effect on behavioural parameters considered, but after subchronic pretreatment by CP 55,940, acute fluoxetine significantly decreased rearing scores and the number of central squares visited, indicated an anxiogenic-like action. These results provide further support to the idea that cannabinoid systems are involved in anxiety-like responses in rats. In addition, they strongly suggest that complex interactions between cannabinoidergic and serotoninergic mechanisms participate in the control of emotion-driven neuronal networks.
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