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Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats.

Publication ,  Journal Article
Moore, NLT; Greenleaf, ALR; Acheson, SK; Wilson, WA; Swartzwelder, HS; Kuhn, CM
Published in: J Pharmacol Exp Ther
November 2010

Adolescence is a well defined developmental period during which marijuana use is common. However, little is known about the response to marijuana in adolescents compared with adults. We have shown previously that adolescent rats are more impaired than adults by Δ(9)-tetrahydrocannabinol (THC), the main psychoactive compound in marijuana, in a spatial learning task, but the mechanism responsible for this differential impairment is not understood. We determined the role of THC tolerance and cannabinoid receptor type 1 (CB1) regulation in THC-induced spatial learning impairment in adolescent and adult rats. We measured the development of tolerance to THC-induced learning impairment in adolescent (postnatal days 30-35) and adult (postnatal days 70-75) rats. We pretreated them for 5 days with 10 mg/kg THC, and then evaluated the effects of vehicle or THC treatment on learning during training in the Morris water maze. We also determined CB1 number and functional coupling in the hippocampus of adolescents and adults. Finally, we measured the time course of hippocampal CB1 desensitization in adolescents and adults during treatment with 10 mg/kg THC or vehicle. Our results indicate that adults, but not adolescents, become tolerant to the effects of THC during water maze training after 5 days of pretreatment. CB1s in adolescent hippocampus are less functionally coupled to G proteins and desensitize more slowly in response to THC treatment than those of adults. THC may impair learning in adolescents more than in adults because of delayed activation of cellular homeostatic adaptive mechanisms underlying cannabinoid tolerance in the hippocampus.

Duke Scholars

Published In

J Pharmacol Exp Ther

DOI

EISSN

1521-0103

Publication Date

November 2010

Volume

335

Issue

2

Start / End Page

294 / 301

Location

United States

Related Subject Headings

  • Spatial Behavior
  • Receptor, Cannabinoid, CB1
  • Rats, Sprague-Dawley
  • Rats
  • Radioligand Assay
  • Protein Binding
  • Pharmacology & Pharmacy
  • Memory
  • Maze Learning
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moore, N. L. T., Greenleaf, A. L. R., Acheson, S. K., Wilson, W. A., Swartzwelder, H. S., & Kuhn, C. M. (2010). Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats. J Pharmacol Exp Ther, 335(2), 294–301. https://doi.org/10.1124/jpet.110.169359
Moore, Nicole L. T., Ashley L. R. Greenleaf, Shawn K. Acheson, Wilkie A. Wilson, H Scott Swartzwelder, and Cynthia M. Kuhn. “Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats.J Pharmacol Exp Ther 335, no. 2 (November 2010): 294–301. https://doi.org/10.1124/jpet.110.169359.
Moore NLT, Greenleaf ALR, Acheson SK, Wilson WA, Swartzwelder HS, Kuhn CM. Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats. J Pharmacol Exp Ther. 2010 Nov;335(2):294–301.
Moore, Nicole L. T., et al. “Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats.J Pharmacol Exp Ther, vol. 335, no. 2, Nov. 2010, pp. 294–301. Pubmed, doi:10.1124/jpet.110.169359.
Moore NLT, Greenleaf ALR, Acheson SK, Wilson WA, Swartzwelder HS, Kuhn CM. Role of cannabinoid receptor type 1 desensitization in greater tetrahydrocannabinol impairment of memory in adolescent rats. J Pharmacol Exp Ther. 2010 Nov;335(2):294–301.
Journal cover image

Published In

J Pharmacol Exp Ther

DOI

EISSN

1521-0103

Publication Date

November 2010

Volume

335

Issue

2

Start / End Page

294 / 301

Location

United States

Related Subject Headings

  • Spatial Behavior
  • Receptor, Cannabinoid, CB1
  • Rats, Sprague-Dawley
  • Rats
  • Radioligand Assay
  • Protein Binding
  • Pharmacology & Pharmacy
  • Memory
  • Maze Learning
  • Male