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Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids.
Eur J Neurosci 2002; 15(12):2057-61EJ

Abstract

It was shown recently that Delta9-tetrahydrocannabinol, like several other drugs eliciting euphoria, stimulates dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens. The aim of the present work was to clarify the mechanism of this stimulatory effect. Our hypothesis was that cannabinoids depress the GABAergic inhibition of dopaminergic neurons in the VTA. Electrophysiological properties of VTA neurons in rat coronal midbrain slices were studied with the patch-clamp technique. GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by electrical stimulation in the vicinity of the recorded neurons. The amplitude of IPSCs was depressed by the synthetic mixed CB1/CB2 cannabinoid receptor agonist WIN55212-2 (10(-6) and 10(-5) m). The CB1 cannabinoid receptor antagonist SR141716A (10(-6) m) prevented the inhibition produced by WIN55212-2 (10(-5) m). Two observations showed that IPSCs were depressed with a presynaptic mechanism. WIN55212-2 (10(-5) m) did not change the amplitude of miniature IPSCs recorded in the presence of tetrodotoxin. Currents evoked by pressure ejection of muscimol from a pipette were also not changed by WIN55212-2 (10(-5) m). The results indicate that activation of CB1 cannabinoid receptors inhibits GABAergic neurotransmission in the VTA with a presynaptic mechanism. Depression of the GABAergic inhibitory input of dopaminergic neurons would increase their firing rate in vivo. Accordingly, dopamine release in the projection region of VTA neurons, the nucleus accumbens, would also increase.

Authors+Show Affiliations

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albertstrasse 25, D-79104 Freiburg i. Br., Germany. szabo@pharmakol.uni-freiburg.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12099913

Citation

Szabo, Bela, et al. "Inhibition of GABAergic Neurotransmission in the Ventral Tegmental Area By Cannabinoids." The European Journal of Neuroscience, vol. 15, no. 12, 2002, pp. 2057-61.
Szabo B, Siemes S, Wallmichrath I. Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci. 2002;15(12):2057-61.
Szabo, B., Siemes, S., & Wallmichrath, I. (2002). Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. The European Journal of Neuroscience, 15(12), pp. 2057-61.
Szabo B, Siemes S, Wallmichrath I. Inhibition of GABAergic Neurotransmission in the Ventral Tegmental Area By Cannabinoids. Eur J Neurosci. 2002;15(12):2057-61. PubMed PMID: 12099913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. AU - Szabo,Bela, AU - Siemes,Sabine, AU - Wallmichrath,Ilka, PY - 2002/7/9/pubmed PY - 2002/9/6/medline PY - 2002/7/9/entrez SP - 2057 EP - 61 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 15 IS - 12 N2 - It was shown recently that Delta9-tetrahydrocannabinol, like several other drugs eliciting euphoria, stimulates dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens. The aim of the present work was to clarify the mechanism of this stimulatory effect. Our hypothesis was that cannabinoids depress the GABAergic inhibition of dopaminergic neurons in the VTA. Electrophysiological properties of VTA neurons in rat coronal midbrain slices were studied with the patch-clamp technique. GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by electrical stimulation in the vicinity of the recorded neurons. The amplitude of IPSCs was depressed by the synthetic mixed CB1/CB2 cannabinoid receptor agonist WIN55212-2 (10(-6) and 10(-5) m). The CB1 cannabinoid receptor antagonist SR141716A (10(-6) m) prevented the inhibition produced by WIN55212-2 (10(-5) m). Two observations showed that IPSCs were depressed with a presynaptic mechanism. WIN55212-2 (10(-5) m) did not change the amplitude of miniature IPSCs recorded in the presence of tetrodotoxin. Currents evoked by pressure ejection of muscimol from a pipette were also not changed by WIN55212-2 (10(-5) m). The results indicate that activation of CB1 cannabinoid receptors inhibits GABAergic neurotransmission in the VTA with a presynaptic mechanism. Depression of the GABAergic inhibitory input of dopaminergic neurons would increase their firing rate in vivo. Accordingly, dopamine release in the projection region of VTA neurons, the nucleus accumbens, would also increase. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/12099913/Inhibition_of_GABAergic_neurotransmission_in_the_ventral_tegmental_area_by_cannabinoids_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0953-816X&date=2002&volume=15&issue=12&spage=2057 DB - PRIME DP - Unbound Medicine ER -