The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to D-9-tetrahydrocannabinol (D 9 -THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28 + ) or adult (post-natal day 60 + ) developmental stages. Adult rats avoided a D 9 -THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final D 9 -THC injection. In contrast, adolescent rats showed no significant place aversion. Adult D 9 -THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent D 9 -THC pretreated rats showed decreased social interaction, while only D 9 -THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last D 9 -THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual D 9 -THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent D 9 -THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in D 9 -THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated D 9 -THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.

There is mounting evidence that chronic cannabis use might result in lasting neurobehavioural changes, although it remains unclear whether vulnerability diminishes with age. The current study compared the effects of cannabinoid exposure at three developmental periods on subsequent measures of memory and anxiety. Male rats aged 4 days (perinatal), 30 days (adolescent) and 56 days (young adult) were injected with vehicle or incremental doses of the cannabinoid receptor agonist CP 55940, daily for 21 consecutive days (0.15, 0.20 or 0.30 mg/kg for 7 days per dose, respectively). Following a 28-day drug-free period, working memory was assessed in an object recognition task. One week later, social anxiety was assessed in a social interaction test. Two days later, generalized anxiety was assessed in an emergence test. Results revealed that CP 55940 impaired working memory and social interaction similarly at all three ages. CP 55940 had no effects in five of six emergence test measures, but a modest but significant reduction in anxiety was noted in one measure following adolescent exposure. We conclude that chronic cannabinoid exposure leads to long-term memory impairments and increased anxiety, irrespective of the age at which drug exposure occurrs.

No abstract

No abstract

The administration of delta9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana, or the endogenous cannabinoid anandamide, has been shown to impair recent memory. The purpose of the present investigation was to determine if the cannabinoid CB1 receptor antagonist SR141716A could attenuate THC- or anandamide-induced memory impairment, and to assess the effects on memory of SR141716A alone. Memory was assessed in rats well-trained in a two-component instrumental discrimination task, consisting of a conditional discrimination, and a non-match-to-position to assess recent or working memory. SR141716A (0.0-2.0 mg/kg) had no effect on either the conditional discrimination or the non-match-to-position. However, SR141716A (0.0-2.0 mg/kg) attenuated the memory impairment produced by THC (2.0 or 4.0 mg/kg) as indexed by an enhancement of performance in the non-match-to-position. When administered to rats pretreated with anandamide (2.0 mg/kg), SR141716A (0.0-2.5 mg/kg) impaired performance in the conditional discrimination at the highest dose. This was interpreted as a deficit in some capacity unrelated to memory (e.g., motor impairment). However, lower doses of SR141716A (0.1 and 0.5 mg/kg) attenuated the anandamide-induced impairment of performance in the non-match-to-position without affecting the conditional discrimination. This is the first report that the memory impairment produced by anandamide can be attenuated by a cannabinoid antagonist; results suggest that anandamide-induced memory disruption is mediated by CB receptors.

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.

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.

No abstract