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Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats.

Publication ,  Journal Article
Kang-Park, M-H; Wilson, WA; Kuhn, CM; Moore, SD; Swartzwelder, HS
Published in: J Neurophysiol
September 2007

The impairment of learning and memory is one of the most powerful and least understood effects of marijuana although the hippocampal formation appears to be one CNS region mediating these effects. We have shown that systemic injection of Delta9-tetrahydrocannabinol (THC), an active component of marijuana, impairs spatial learning more efficaciously in adolescent rats, compared with adult rats, but there have been no studies of the cellular mechanisms underlying this developmental sensitivity. In this study, we examined cannabinoid-mediated activity in hippocampal area CA1 neurons in brain slices from adolescent and adult rats. The magnitude of endocannabinoid-mediated synaptic functions such as long-term depression of inhibition was greater in the hippocampal slices from adolescent rats than in those from adults. The effect of R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazine-6-yl)(1-naphtalenyl) methanone mesylate (WIN55,212-2), an exogenous cannabinoid agonist, to suppress GABA(A) receptor-mediated synaptic responses was also greater in the hippocampal slices from adolescent rats than in those from adults. However, tonic endocannabinoid effects, shown as an increase of the spontaneous IPSC frequency by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a specific CB1 receptor antagonist, were greater in CA1 neurons from adult rats than in those from adolescent rats. On the other hand, WIN55,212-2 suppressed glutamate-mediated excitatory neurotransmission in CA1 pyramidal cells from adolescent and adult rats with similar efficacy. These results indicate that inhibitory synaptic function in the adolescent hippocampus is more sensitive to cannabinoid effects and may account, in part, for the greater sensitivity of adolescent animals to THC-induced memory impairment.

Duke Scholars

Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

September 2007

Volume

98

Issue

3

Start / End Page

1223 / 1230

Location

United States

Related Subject Headings

  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Rats
  • Quinoxalines
  • Neurology & Neurosurgery
  • Male
  • Inhibitory Postsynaptic Potentials
  • In Vitro Techniques
  • Hippocampus
  • Excitatory Postsynaptic Potentials
 

Citation

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MLA
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Kang-Park, M.-H., Wilson, W. A., Kuhn, C. M., Moore, S. D., & Swartzwelder, H. S. (2007). Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats. J Neurophysiol, 98(3), 1223–1230. https://doi.org/10.1152/jn.00091.2007
Kang-Park, Maeng-Hee, Wilkie A. Wilson, Cynthia M. Kuhn, Scott D. Moore, and H Scott Swartzwelder. “Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats.J Neurophysiol 98, no. 3 (September 2007): 1223–30. https://doi.org/10.1152/jn.00091.2007.
Kang-Park M-H, Wilson WA, Kuhn CM, Moore SD, Swartzwelder HS. Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats. J Neurophysiol. 2007 Sep;98(3):1223–30.
Kang-Park, Maeng-Hee, et al. “Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats.J Neurophysiol, vol. 98, no. 3, Sept. 2007, pp. 1223–30. Pubmed, doi:10.1152/jn.00091.2007.
Kang-Park M-H, Wilson WA, Kuhn CM, Moore SD, Swartzwelder HS. Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats. J Neurophysiol. 2007 Sep;98(3):1223–1230.

Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

September 2007

Volume

98

Issue

3

Start / End Page

1223 / 1230

Location

United States

Related Subject Headings

  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Rats
  • Quinoxalines
  • Neurology & Neurosurgery
  • Male
  • Inhibitory Postsynaptic Potentials
  • In Vitro Techniques
  • Hippocampus
  • Excitatory Postsynaptic Potentials