Neuroscience 2004 Abstract
| Presentation Number: | 728.13 |
|---|---|
| Abstract Title: | Developmental exposure to cannabinoids increases subsceptibility to ethanol-induced apoptotic neurodegeneration in the neonatal rat brain. |
| Authors: |
Krutz, B.*1
; Sifringer, M.1
; Bittigau, P.1
; Pragst, F.2
; Felderhoff-Mueser, U.3
; Ikonomidou, C.1
; Hansen, H.1
1Ped. Neurol. and Neurosci. Res. Ctr., Charite, Humboldt Univ., Berlin, Germany 2Inst. of Legal Med., Charite, Humboldt Univ., Berlin, Germany 3Neonatology, Charite, Humboldt Univ., Berlin, Germany |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Trophic factors and cell death |
| Session: |
728. Trophic Factors and Cell Death III Poster |
| Presentation Time: | Tuesday, October 26, 2004 1:00 PM-2:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # F28 |
| Keywords: | APOPTOSIS, CELL DEATH, NEUROTOXICITY, CANNABINOIDS |
Marijuana is the most widely used illicit drug among women of reproductive age. Neurocognitive deficits have been reported in children whose mothers used marijuana during pregnancy. Maternal consumption of alcohol during pregnancy has long been known to cause serious developmental deficits depending on the amount and timing of exposure during gestation.
Here we report that acute administration of Δ9-tetrahydrocannabinol (THC, 1-10 mg/kg), the principal psychoactive cannabinoid of marijuana, has pro-apoptotic properties in the neonatal rat brain when co-administered with a subtoxic dose of ethanol (1.1 g/kg). THC did not induce neurodegeneration when administered alone. Neuronal degeneration became disseminated and very severe when THC was combined with a mildly intoxicating ethanol dose (1.5 g/kg), with the effect of this drug combination qualitatively and quantitatively resembling the massive apoptotic death observed when administering ethanol alone at much higher doses. THC did not influence plasma ethanol levels. The detrimental effect of THC was mimicked by the synthetic cannabinoid WIN 55,212-2 (1-10 mg/kg) and counteracted by the CB1 receptor antagonist SR141716A (0.4 mg/kg). THC enhanced the pro-apoptotic effect of phenobarbital and MK801. These observations indicate that CB1 receptor activation primes the developing rat brain to suffer apoptotic brain damage by positively modulating GABAergic or by dampening glutamatergic neurotransmission. This neurodepressant effect of cannabinoids may have important implications in understanding the mechanisms underlying cannabinoid-induced developmental neurotoxicity.
Supported by The Alfred Benzon Foundation and a Humboldt University grant.
Here we report that acute administration of Δ9-tetrahydrocannabinol (THC, 1-10 mg/kg), the principal psychoactive cannabinoid of marijuana, has pro-apoptotic properties in the neonatal rat brain when co-administered with a subtoxic dose of ethanol (1.1 g/kg). THC did not induce neurodegeneration when administered alone. Neuronal degeneration became disseminated and very severe when THC was combined with a mildly intoxicating ethanol dose (1.5 g/kg), with the effect of this drug combination qualitatively and quantitatively resembling the massive apoptotic death observed when administering ethanol alone at much higher doses. THC did not influence plasma ethanol levels. The detrimental effect of THC was mimicked by the synthetic cannabinoid WIN 55,212-2 (1-10 mg/kg) and counteracted by the CB1 receptor antagonist SR141716A (0.4 mg/kg). THC enhanced the pro-apoptotic effect of phenobarbital and MK801. These observations indicate that CB1 receptor activation primes the developing rat brain to suffer apoptotic brain damage by positively modulating GABAergic or by dampening glutamatergic neurotransmission. This neurodepressant effect of cannabinoids may have important implications in understanding the mechanisms underlying cannabinoid-induced developmental neurotoxicity.
Supported by The Alfred Benzon Foundation and a Humboldt University grant.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
Copyright © 2004-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
