Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats

Abstract

Although many studies have examined the acute behavioural effects of cannabinoids in rodents, few have examined the lasting effects of cannabinoids at different developmental ages. This study compared lasting effects of cannabinoid exposure occurring in adolescence to that occurring in early adulthood. Forty, 30-day old (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected with vehicle or incremental doses of the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 microg/kg i.p. for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working memory was assessed using an object recognition task. Locomotor activity was also measured in the object recognition apparatus via a ceiling-mounted passive infrared sensor. Three days later, anxiety was assessed using a social interaction test. In the object recognition task, significantly poorer working memory was observed in the adolescent but not adult CP 55,940-treated rats. Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant decrease in social interaction with a novel conspecific. These results suggest that chronic exposure to a cannabinoid receptor agonist well after the immediate postnatal period, but before reaching sexual maturity, can lead to increased anxiety and a lasting impairment of working memory.

Adolescent Exposure of JWH-018 “Spice” Produces Subtle Effects on Learning and Memory Performance in Adulthood

“…Consistent with this are reports of working memory impairments in adolescent but adult rats exposed to Δ9-THC when subsequently tested in adulthood [13,14]. However, the issue remains open for further inquiry as the residual effects associated with adolescent exposure are not always found [15].…”

“…Last, CP 55940 exposure during adolescence produced a number of behavioral effects when measured in adulthood, with sex differences also observed [35]. Working memory deficits after adolescent exposure have also been found [15]. To reiterate, the timing of the drug exposure may very well produce different but long-lasting effects.…”

“…In rats, the timing of the exposure during the neurophysiological development of the organism appears to contribute to impairments in working memory when tested as adults while adult Δ-9-THC-treated rats does not produce persistent impairments [13,14]. Last, such adolescent exposure effects may, in part, be associated with the sex of the animal as well, with more severe effects reported in female rats [15].…”

Gone to Pot – A Review of the Association between Cannabis and Psychosis

“…A large meta-analysis of 83 studies found that the age of onset of psychosis in cannabis users was 2.7 years younger than in non-users (252). Animal studies have shown that exposure to cannabinoids in adolescence has more deleterious effects than exposure in adulthood (253–257). …”

“…These studies suggest a “window of vulnerability” hypothesis: a critical period during early adolescence where the brain is particularly susceptible to the psychosis-inducing effects of cannabis (19, 250, 251, 253–258). One possible explanation for the “window of vulnerability” theory is that cannabis may affect the brain during a critical period of development and maturation.…”