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 CB(1) 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.
Bambico
Francis Rodriguez
FR
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Canada H3A1A1.
Nguyen
Nhu-Tram
NT
Katz
Noam
N
Gobbi
Gabriella
G
D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D048588:Benzoxazines / Q000633:toxicity; D015306:Biogenic Monoamines / Q000819:agonists* / Q000037:antagonists & inhibitors*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000633:toxicity; D002186:Cannabinoids / Q000633:toxicity*; D003866:Depressive Disorder / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D001523:Mental Disorders / Q000139:chemically induced* / Q000378:metabolism; D009025:Morpholines / Q000633:toxicity; D009281:Naphthalenes / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013995:Time
D048588:Benzoxazines; D015306:Biogenic Monoamines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D012701:Serotonin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009638:Norepinephrine