Andrew R Abela1,2,3, Arya Rahbarnia4,5, Suzanne Wood5, Anh D Lê4,6, Paul J Fletcher4,7,5. 1. Preclinical Research and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, Ontario, M5T 1R8, Canada. andrew.abela@camh.ca. 2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. andrew.abela@camh.ca. 3. Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON, M5T 1R8, Canada. andrew.abela@camh.ca. 4. Preclinical Research and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, Ontario, M5T 1R8, Canada. 5. Department of Psychology, University of Toronto, Toronto, ON, Canada. 6. Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada. 7. Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Abstract
RATIONALE AND OBJECTIVES: Adolescence is a sensitive period of brain development, during which there may be a heightened vulnerability to the effects of drug use. Despite this, the long-term effects of cannabis use during this developmental period on cognition are poorly understood. METHODS: We exposed adolescent rats to escalating doses of Δ9-tetrahydrocannabinol (THC)-the primary psychoactive component of cannabis-or vehicle solution during postnatal days (PND) 35-45, a period of development that is analogous to human adolescence (THC doses: PND 35-37, 2.5 mg/kg; PND 38-41, 5 mg/kg; PND 42-45, 10 mg/kg). After a period of abstinence, in adulthood, rats were tested on an automated touchscreen version of a paired-associates learning (PAL) task to assess their ability to learn and recall object-location associations. Prepulse inhibition (PPI) of the startle response was also measured at three time points (5 days, 4 months, and 6 months after exposure) to assess sensorimotor gating, the ability to filter out insignificant sensory information from the environment. RESULTS: Compared to rats exposed to vehicle alone, rats exposed to THC during adolescence took longer to learn the PAL task when tested in adulthood, even when trials contained visually identical stimuli that differed only in location. Despite this, no differences were observed later in testing, when trials contained visually distinct stimuli in different locations. Rats exposed to THC also displayed impairments in sensorimotor gating, as measured by prepulse inhibition of the startle response, though this deficit did appear to decrease over time. CONCLUSION: Taken together, THC exposure during adolescence produces long-term deficits in associative learning and sensorimotor gating, though the impact of these deficits seems to diminish with time. Thus, adolescence may represent a period of neurocognitive development that is vulnerable to the harms of cannabis use, though the stability of such harms is uncertain.
RATIONALE AND OBJECTIVES: Adolescence is a sensitive period of brain development, during which there may be a heightened vulnerability to the effects of drug use. Despite this, the long-term effects of cannabis use during this developmental period on cognition are poorly understood. METHODS: We exposed adolescent rats to escalating doses of Δ9-tetrahydrocannabinol (THC)-the primary psychoactive component of cannabis-or vehicle solution during postnatal days (PND) 35-45, a period of development that is analogous to human adolescence (THC doses: PND 35-37, 2.5 mg/kg; PND 38-41, 5 mg/kg; PND 42-45, 10 mg/kg). After a period of abstinence, in adulthood, rats were tested on an automated touchscreen version of a paired-associates learning (PAL) task to assess their ability to learn and recall object-location associations. Prepulse inhibition (PPI) of the startle response was also measured at three time points (5 days, 4 months, and 6 months after exposure) to assess sensorimotor gating, the ability to filter out insignificant sensory information from the environment. RESULTS: Compared to rats exposed to vehicle alone, rats exposed to THC during adolescence took longer to learn the PAL task when tested in adulthood, even when trials contained visually identical stimuli that differed only in location. Despite this, no differences were observed later in testing, when trials contained visually distinct stimuli in different locations. Rats exposed to THC also displayed impairments in sensorimotor gating, as measured by prepulse inhibition of the startle response, though this deficit did appear to decrease over time. CONCLUSION: Taken together, THC exposure during adolescence produces long-term deficits in associative learning and sensorimotor gating, though the impact of these deficits seems to diminish with time. Thus, adolescence may represent a period of neurocognitive development that is vulnerable to the harms of cannabis use, though the stability of such harms is uncertain.
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