Impact of repeated exposure to hormonal contraceptives during adolescence on cannabinoid-induced behavior in female rats

Cannabis is still the most used drug worldwide, with a number of adolescent female users that has gradually increased over the last decade. Hormonal contraceptives (HC) continue to be the most commonly used form of prescription contraceptives used by adolescents in many countries, and evidence is mixed regarding any increased health risk for the concomitant use of drugs of abuse. HC block ovulation by reducing the levels of estradiol and progesterone, two hormones that within the brain modulate emotional states, cognitive processes and reward. We have previously demonstrated that chronic treatment with HC induces anxiety, reduces social behavior and sex motivation and affects memory processes in female rats. In this study we tested the hypothesis that long-term adolescent treatment with ethinyl estradiol (EE, 0.030 mg) plus levonorgestrel (LNG, 0.125 mg), two of the most widely used steroids in the HC pill, may interfere with the behavioral effects induced by the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) in female rats. Specifically, we evaluated the effects of a repeated intravenous administration of WIN at the dose of 12.5 ?g/kg/0.1ml, known to activate the brain reward system, on (i) motor activity, (ii) emotional reactivity, (iii) social behavior, (iv) cognitive functions and (v) plasma levels of estrogen and progesterone of HC-exposed and vehicle-exposed (control) females. Translated at the human level, our findings contribute to verify the hypothesis that young women using HC are differently vulnerable to cannabis-induced behavioral effects and that cannabis alters the emotional states and cognitive functions of adolescents using HC.