Abstract
Recently, we have shown that acamprosate is able to modulate extracellular dopamine (DA) levels in the nucleus accumbens (NAc) and may act as an antagonist of N-methyl-D-aspartate (NMDA) receptors. Neurochemical studies show that chemical stimulation (using NMDA) of the ventral subiculum (vSub) of the hippocampus produces robust and sustained increases in extracellular DA levels in the NAc, an effect mediated through ionotropic glutamate (iGlu) receptors. The present study examines whether acamprosate locally infused in the NAc of rats could block or attenuate the increase in NAc extracellular DA elicited by chemical stimulation (with 5 mM NMDA) of the ventral subiculum of the hippocampus. The stimulation of the vSub during perfusion of artificial cerebrospinal fluid in NAc induced a significant and persistent increase in NAc DA levels. Reverse dialysis of 0.05 mM acamprosate in NAc blocked the increase in DA evoked by the chemical stimulation of the vSub. These data support the possibility that the antagonism at the NMDA receptors in NAc can explain, at least in part, the mechanism of action of this drug.
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References
Blaha CD, Yang CR, Floresco SB, Barr AM, Phillips A (1997) Stimulation of the ventral subiculum of the hippocampus evokes glutamate receptor-mediated changes in dopamine efflux in the rat nucleus accumbens. Eur J Neurosci 9:902–911
Brudzynski SM, Gibson CJ (1997) Release of dopamine in the nucleus accumbens caused by stimulation of the subiculum in freely moving rats. Brain Res Bull 42:303–308
Cano-Cebrián MJ, Zornoza-Sabina T, Guerri C, Polache A, Granero L (2003) Local acamprosate modulates dopamine release in the rat nucleus accumbens through NMDA receptors: an in vivo microdialysis study. Naunyn-Schmiedebergs Arch Pharmacol 367:119–125
Cornish JL, Kalivas PW (2000) Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 20:RC89
Cornish JL, Duffy P, Kalivas PW (1999) A role for glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93:1359–1367
Floresco SB, Todd CL, Grace AA (2001) Glutamatergic afferents from the hippocampus to the nucleus accumbens regulate activity of ventral tegmental area dopamine neurons. J Neurosci 21:4915–4922
Groenewegen HJ, Vermeulen-Van der Zee E, Te Kortschot A, Witter MP (1987) Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin. Neuroscience 23:103–120
Legault M, Wise R (1999) Injections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens. Synapse 31:241–249
Legault M, Rompré PP, Wise R (2000) Chemical stimulation of the ventral hippocampus elevates nucleus accumbens dopamine by activating dopaminergic neurons of the ventral tegmental area. J Neurosci 20:1635–1642
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New York
Taepavarapruk P, Phillips A (2003) Neurochemical correlates of relapse to d-amphetamine self-administration by rats induced by stimulation of the ventral subicullum. Psychopharmacology 168:99–108
Taepavarapruk P, Floresco SB, Phillips A (2000) Hyperlocomotion and increased dopamine efflux in the rat nucleus accumbens evoked by electrical stimulation of the ventral subiculum: role of ionotropic glutamate and dopamine D1 receptors. Psychopharmacology 151:242–251
Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL (2001) Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292:1175–1178
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Cano-Cebrián, M.J., Zornoza-Sabina, T., Guerri, C. et al. Acamprosate blocks the increase in dopamine extracellular levels in nucleus accumbens evoked by chemical stimulation of the ventral hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 368, 324–327 (2003). https://doi.org/10.1007/s00210-003-0795-3
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DOI: https://doi.org/10.1007/s00210-003-0795-3