Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission

The pathophysiological neural mechanism underlying the depressogenic and anxiogenic effects of chronic adolescent cannabinoid use may be linked to perturbations in monoaminergic neurotransmission. We tested this hypothesis by administering the CB1 receptor agonist WIN55,212-2, once daily for 20 days to adolescent and adult rats, subsequently subjecting them to tests for emotional reactivity paralleled by the in vivo extracellular recordings of serotonergic and noradrenergic neurons. Chronic adolescent exposure but not adult exposure to low (0.2 mg/kg) and high (1.0 mg/kg) doses led to depression-like behaviour in the forced swim and sucrose preference test, while the high dose also induced anxiety-like consequences in the novelty-suppressed feeding test. Electrophysiological recordings revealed both doses to have attenuated serotonergic activity, while the high dose also led to a hyperactivity of noradrenergic neurons only after adolescent exposure. These suggest that long-term exposure to cannabinoids during adolescence induces anxiety-like and depression-like behaviours in adulthood and that this may be instigated by serotonergic hypoactivity and noradrenergic hyperactivity.