Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors.
Acamprosate (calciumacetylhomotaurinate) is used therapeutically against relapse in weaned alcoholics. In the present study, the mechanism of action was investigated by making intracellular in vitro and extracellular in vivo recordings from rat neocortical neurons. Acamprosate (0.1-1 mM) added to the perfusion fluid in vitro reduced excitatory and inhibitory postsynaptic potentials and the depolarizing responses evoked by iontophoretic application of the excitatory amino acids, L-glutamate, L-aspartate, L-homocysteate and N-methyl-D-aspartate, but did not alter the responses to gamma-aminobutyric acid. Acamprosate decreased electrical excitability without apparently changing membrane potential, input resistance, afterhyperpolarization, or threshold and amplitude of the action potential. In vivo iontophoretic application of acamprosate reduced the extracellularly recorded unit activity elicited by iontophoretically applied L-glutamate, whereas spontaneous discharges remained unaffected. These data suggest that acamprosate reduces the postsynaptic efficacy of excitatory amino acid neurotransmitters and lowers neuronal excitability in the neocortex of the rat.
Zeise
M L
ML
Max-Planck-Institute of Psychiatry, Clinical Institute, Munich, Germany.
Kasparov
S
S
Capogna
M
M
Zieglgänsberger
W
W
D000077443:Acamprosate; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017459:Receptors, Amino Acid / Q000187:drug effects*; D013569:Synapses / Q000502:physiology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D017459:Receptors, Amino Acid; D013654:Taurine; D000077443:Acamprosate