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

Francis Rodriguez Bambico; Nhu-Tram Nguyen; Noam Katz; Gabriella Gobbi

doi:10.1016/j.nbd.2009.11.020

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

Neurobiol Dis. 2010 Mar;37(3):641-55. doi: 10.1016/j.nbd.2009.11.020. Epub 2009 Dec 5.

Authors

Francis Rodriguez Bambico¹, Nhu-Tram Nguyen, Noam Katz, Gabriella Gobbi

Affiliation

¹ Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Canada H3A1A1.

PMID: 19969082
DOI: 10.1016/j.nbd.2009.11.020

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aging / physiology
Animals
Animals, Newborn
Anxiety Disorders / chemically induced
Anxiety Disorders / metabolism
Anxiety Disorders / physiopathology
Behavior, Animal / drug effects
Behavior, Animal / physiology
Benzoxazines / toxicity
Biogenic Monoamines / agonists*
Biogenic Monoamines / antagonists & inhibitors*
Brain / drug effects*
Brain / growth & development
Brain / metabolism
Brain Chemistry / drug effects
Brain Chemistry / physiology
Calcium Channel Blockers / toxicity
Cannabinoids / toxicity*
Depressive Disorder / chemically induced
Depressive Disorder / metabolism
Depressive Disorder / physiopathology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Emotions / drug effects
Emotions / physiology
Male
Marijuana Abuse / metabolism
Marijuana Abuse / physiopathology*
Marijuana Abuse / psychology
Mental Disorders / chemically induced*
Mental Disorders / metabolism
Morpholines / toxicity
Naphthalenes / toxicity
Norepinephrine / metabolism
Rats
Rats, Sprague-Dawley
Serotonin / metabolism
Synaptic Transmission / drug effects
Synaptic Transmission / physiology
Time

Substances

Benzoxazines
Biogenic Monoamines
Calcium Channel Blockers
Cannabinoids
Morpholines
Naphthalenes
Serotonin
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
Norepinephrine