Abstract
The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9-tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to a sub-threshold dose of d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.
Highlights
Marijuana is one of the most commonly used drugs of abuse worldwide1, and the psychoactive properties of marijuana are a result of the actions of ∆9-tetrahydrocannabinol (THC)2,3
Chronic marijuana use is associated with an increased risk of psychosis and depression4, and these relationships are even more concerning when use occurs during adolescence
A dose of 1mg/kg d-amphetamine was used to confirm previous experiments and did induce significant place preference, 0.7mg/kg dose was considered subthreshold for all subsequent experiments
Summary
Marijuana is one of the most commonly used drugs of abuse worldwide, and the psychoactive properties of marijuana are a result of the actions of ∆9-tetrahydrocannabinol (THC). Chronic marijuana use is associated with an increased risk of psychosis and depression, and these relationships are even more concerning when use occurs during adolescence (for example, 5–7). In addition to the reported increased sensitivity of the adolescent period to the effects of marijuana, sex may play a role in the consequences of both short- and long-term marijuana use with females more sensitive to depression and anxiety following marijuana exposure in adolescence. In addition to sex differences in the outcome of adolescent marijuana use, genetic background, including rat strain, can change the long-term consequences of THC exposure. Given that rat strains are used interchangeably in drug abuse research despite their innate differences, the inclusion of multiple strains of rat in any one study can help determine the strength and reproducibility of the long-term consequences of marijuana
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