TY - JOUR
T1 - Despite strong behavioral disruption, Δ9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus
AU - Kochman, Linda J.
AU - dos Santos, Angela Amancio
AU - Fornal, Casimir A.
AU - Jacobs, Barry L.
N1 - Funding Information:
This work was supported by National Institute on Drug Abuse Grant DA016976. AAS was a recipient of a Sandwich Fellowship [CNPq200924/03-6(NV)] from the Brazilian Government. The authors wish to thank Dr. Todd Weber for providing the activity measurements, Joanne Stevens and Sherry Zhang for their excellent technical assistance, and NIDA for kindly providing the THC for this study.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/10/3
Y1 - 2006/10/3
N2 - Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Δ9-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2′-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.
AB - Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Δ9-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2′-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.
KW - BrdU
KW - Cannabinoid
KW - Hippocampus
KW - Marijuana
KW - Neurogenesis
UR - http://www.scopus.com/inward/record.url?scp=33748864050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748864050&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2006.07.080
DO - 10.1016/j.brainres.2006.07.080
M3 - Article
C2 - 16930565
AN - SCOPUS:33748864050
SN - 0006-8993
VL - 1113
SP - 86
EP - 93
JO - Brain Research
JF - Brain Research
IS - 1
ER -