Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters

The aim of the present study was to examine the effects of the cannabinoid agonist CP 55,940 and the antagonist SR 141716A, alone and in combination, on rat exploratory and anxiety-like behaviour in the holeboard and elevated plus-maze tests. A further aim was to evaluate the effects of these treatm ents on hypothalamic neurotransmitters. Animals treated with CP 55,940 dose s of 0.125 and 0.1 mg/kg exhibited less exploration and an increase in anxi ety-like behaviour accompanied by great motor inhibition. No hypoactivity w as seen at 0.075 mg/kg dosage, but anxiety and neophobic responses persiste d, indicating independent and specific effects. Motor activity effects indu ced by CP 55,940 were reversed by pretreatment with SR 141716A (3 mg/kg). S urprisingly, when administered on its own, the antagonist also induced a re duction in exploratory parameters and an increase in anxiety-like responses . These apparently similar effects might be caused by different neural mech anisms. Finally, CP 55,940 increased hypothalamic dopamine and serotonin le vels. These increases might be involved in the activation of the hypothalam ic-pituitary-adrenal axis described for cannabinoids. (C) 2001 Elsevier Sci ence Inc. All rights reserved.