Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood.
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.
Rubino
Tiziana
T
DBSF and Neuroscience Center, University of Insubria, Busto Arsizio, VA, Italy. tiziana.rubino@uninsubria.it
Realini
Natalia
N
Braida
Daniela
D
Guidi
Sandra
S
Capurro
Valeria
V
Viganò
Daniela
D
Guidali
Cinzia
C
Pinter
Marta
M
Sala
Mariaelvina
M
Bartesaghi
Renata
R
Parolaro
Daniela
D
D000375:Aging / Q000187:drug effects; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000139:chemically induced*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D000076122:Disks Large Homolog 4 Protein; D013759:Dronabinol / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011619:Psychotropic Drugs; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; C488416:Tubb3 protein, rat; D014404:Tubulin; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; D013759:Dronabinol