ABSTRACT
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor-channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5-HT3 ligand-gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol-induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage-operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.
Subject(s)
Calcium Channels/drug effects , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Receptors, AMPA/drug effects , Receptors, Metabotropic Glutamate/drug effects , Receptors, N-Methyl-D-Aspartate/drug effects , Animals , Calcium Channels/physiology , Hippocampus/drug effects , Hippocampus/physiology , Humans , Ion Channels/drug effects , Ion Channels/physiology , Receptors, AMPA/physiology , Receptors, Metabotropic Glutamate/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Receptors, Serotonin/drug effects , Receptors, Serotonin/physiology , Receptors, Serotonin, 5-HT3 , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/metabolismABSTRACT
Microdialysis of the ventral tegmental area in conscious rats was used to evaluate the influence of opioids and GABA agonists on extracellular levels of GABA and somatodendritically released dopamine. The administration of morphine through the dialysis probe elicited significant, dose-dependent increases in the levels of extracellular dopamine and significantly reduced the extracellular concentration of GABA. In contrast, a dose-dependent decrease in somatodendritic extracellular dopamine was produced following the administration of the GABAB agonist baclofen. The increase in dopamine levels elicited by morphine (100 microM) was completely blocked by either baclofen (100 microM) coadministration or peripheral injection of naloxone (2 mg/kg, i.p.). Application of the GABAA agonist muscimol produced a significant increase in both extracellular levels of dopamine and locomotor activity. The present results, together with other electrophysiological, neurochemical, and behavioral data, support a hypothesis that stimulation of mu-opioid or GABAA receptors inhibits the activity of GABAergic afferents to dopamine neurons, thereby removing tonic inhibitory regulation, whereas stimulation of GABAB receptors directly inhibits dopamine neurons.
Subject(s)
Dendrites/physiology , Dopamine/metabolism , Morphine/pharmacology , Naloxone/pharmacology , Neurons/physiology , Tegmentum Mesencephali/physiology , gamma-Aminobutyric Acid/pharmacology , Afferent Pathways/physiology , Animals , Baclofen/pharmacology , Biological Transport , Dendrites/drug effects , Dialysis/methods , Dopamine/analysis , Dose-Response Relationship, Drug , Interneurons/physiology , Kinetics , Male , Models, Neurological , Morphine/metabolism , Muscimol/pharmacology , Neurons/drug effects , Rats , Rats, Inbred Strains , Receptors, GABA-A/drug effects , Receptors, GABA-A/physiology , Tegmentum Mesencephali/drug effects , Time FactorsABSTRACT
Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.
