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

Tiziana Rubino, Natalia Realini, Daniela Braida, Sandra Guidi, Valeria Capurro, Daniela Viganò, Cinzia Guidali, Marta Pinter, Mariaelvina Sala, Renata Bartesaghi, Daniela Parolaro

Hippocampus August 2009 DOI: 10.1002/hipo.20554 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Adolescent rats
Intervention Delta9-tetrahydrocannabinol (THC)
Duration Treatment from postnatal days 35 to 45, testing at postnatal day 75
Measures passive avoidance task, radial maze task, Golgi-Cox staining
Topics Cannabis Neuroplasticity
Key findings Adolescent THC exposure impaired spatial working memory in adulthood, with reduced hippocampal protein markers (GFAP, VAMP2, PSD95, NMDA receptors) and dendritic complexity, suggesting lasting neuroplastic changes.

Abstract

Marijuana and hashish are the illicit drugs most frequently used by human adolescents. Given the continued neurodevelopment throughout adolescence, adolescents may be more vulnerable than adults to certain neural consequences of heavy marijuana use. This study aimed to assess whether an experimental model of adolescent chronic exposure to Delta9-tetrahydrocannabinol (THC), may induce lasting effects on learning and memory. Adolescent rats have been treated with THC or its vehicle from 35 to 45 postnatal days (PND) and left undisturbed until their adulthood (75 PND) when aversive and spatial memory was assessed using the passive avoidance and radial maze tasks. No alteration was found in aversive memory, but in the radial maze THC pretreated animals exhibited a worse performance than vehicles, suggesting a deficit in spatial working memory. To correlate memory impairment to altered neuroplasticity, level of marker proteins was investigated in the hippocampus, the most relevant area mediating spatial memory. A significant decrease in the astroglial marker glial fibrillar acid protein was found as well as in pre- and postsynaptic protein expression (VAMP2, PSD95) and NMDA receptor levels in pretreated rats. To parallel these changes to alteration in dendritic morphology, Golgi-Cox staining was performed in the hippocampal dentate gyrus. Pretreated rats had a significantly lower total dendritic length and number than vehicles, as well as reduced spine density. Our data suggest that THC pretreated rats may establish less synaptic contacts and/or less efficient synaptic connections throughout the hippocampus and this could represent the molecular underpinning of the cognitive deficit induced by adolescent THC treatment.

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