Sex differences in the effects of Δ9-tetrahydrocannabinol on spatial learning in adolescent and adult rats

Abstract

Like other recreational drugs, cannabinoids may produce different effects in men and women. In this study we measured the effects of delta9-tetrahydrocannabinol (THC) on spatial learning in two groups that are underrepresented in drug research--females and adolescents. In the first experiment, adolescent (postnatal day 30) and adult (postnatal day 70) rats of both sexes were treated subchronically with 5.0 mg/kg THC or vehicle for five consecutive days. Thirty minutes after each daily injection, they were tested on the spatial version of the Morris water maze task. In the second experiment, a separate group of adolescent and adult rats of both sexes was treated with 5.0 mg/kg THC or vehicle daily for 21 days and tested, 4 weeks later, on the spatial version of the water maze. Subchronic THC impaired spatial learning, and this effect was dependent upon both the age and sex of the animals tested. Prior exposure to chronic THC, however, did not cause any long-lasting spatial learning deficits. On the basis of our previous studies in male rats the third experiment assessed the dose-response relationship for the effects of THC on spatial learning and memory in female animals. We found that subchronic THC treatment (2.5, 5.0, or 10.0 mg/kg, intraperitoneally) disrupted learning in both adolescents and adults, but with greater effects at higher doses in adolescents compared with adults. The developmental sensitivity to subchronic THC confirms previous work carried out in our laboratory, and the sex-dependent effects highlight the importance of including females in drug abuse and addiction research.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

“…In these regards, cannabis exhibits similar properties with other drugs of abuse, namely rewarding effects with initial use. However, like opiates and unlike ethanol, cocaine, amphetamine, and nicotine, acute administration of THC and cannabidiol have been shown to disrupt hippocampus-dependent spatial learning in the Morris water maze and radial arm maze (Lichtman et al 1995;Lichtman and Martin 1996;Da Silva and Takahashi 2002;Cha et al 2007;Niyuhire et al 2007) as well as contextual fear conditioning (Lemos et al 2010;Stern et al 2012). In line with the animal studies, human studies also suggest that acute cannabinoids result in impaired memory (Tinklenberg et al 1970;Ferraro 1980; for review, see Ranganathan and D'Souza 2006).…”

Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior

“…In adulthood, females are more susceptible to cannabinoidinduced antinociception, locomotion, and memory deficits (29,30). Thus far, the majority of sex differences in the endocannabinoid system or cannabinoid-induced behavioral effects have been attributed to fluctuations in gonadal steroid levels (31, 32).…”

Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood

“…The acute effect of cannabis on learning and memory is well-known (Riedel and Davies, 2005;Ranganathan and D'souza, 2006), however literature regarding long-term cognitive effects of adolescent cannabinoid exposure is scarce and not always in accordance, depending on the compound administered, the treatment paradigm used and the cognitive task performed. Adolescent exposure to THC, the natural cannabinoid agonist, has been shown to induce both impaired memory (Quinn et al, 2008), and no lasting learning deficits in adult rats (Cha et al, 2006(Cha et al, , 2007. However, when synthetic cannabinoid agonists were used in adolescent rats, impaired recognition memory was observed in adulthood Koch, 2003, 2007;O'shea et al, 2004.…”