title: Dopamine release in the nucleus accumbens and latent inhibition in the rat following microinjections of a 5-HT1B agonist into the dorsal subiculum: implications for schizophrenia.
abstract: Microinjection of a serotonergic 5-HT1B agonist (S-CM-GTNH2, 3 microg/l) into the dorsal subiculum (DS) induced long-lasting increases in dopamine (DA; +58%), dihydroxyphenylacetic acid (DOPAC; +15%) and homovanillic acid (HVA; +31%), without changing extracellular levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), measured by microdialysis in freely moving rats in the shell area of the nucleus accumbens (n. acc). Perfusion of a glutamate-N-methyl-D-aspartate (NMDA) receptor antagonist (MK 801, dizocilpine, 10 microM) through the dialysis probe in the n. acc induced similar long-lasting increases in DA and DOPAC, whereas the glutamate-quisqualate/kainate receptor antagonist (CNQX, 50 microM) had no effect. In the presence of dizocilpine in the n. acc, microinjection of S-CM-GTNH2 into the DS could still increase DOPAC and HVA, but DA levels were not further changed, whereas in the presence of CNQX, microinjection of S-CM-GTNH2 into the DS still increased not only DOPAC and HVA, but also DA levels in a way similar to that in the absence of glutamate antagonist. Therefore, activation of 5-HT1B receptors located in the DS increases the release of DA in the n. acc, presumably via the glutamatergic projection to this structure and acting through NMDA receptors in it. This implies either the suppression of a tonic indirect inhibitory influence and/or stimulation of a phasic excitatory effect of glutamate. Disruption of latent inhibition (LI) has been suggested as a model for a cognitive deficit in schizophrenia (hyperattention to irrelevant stimuli) and is usually associated with an increase in DA release in the n. acc. However, s.c. injection of RU 24 969 (0.5 mg/kg), a mixed 5-HT1A-5-HT1B agonist, which was previously shown to increase DA release in the n. acc, left LI unchanged. Moreover, bilateral microinjections of S-CM-GTNH2 into the rat DS tended to potentiate LI, in spite of the increase in DA in n. acc demonstrated here. It is concluded that not all increases in DA release in the n. acc are functionally equivalent. Sensitization of receptors or impulse-dependent increase in DA release might be necessary to disrupt LI. The possible role of altered serotonergic transmission, through h5-HT1B receptors (human homologue of the rat 5-HT1B receptors) located in the DS, in acute schizophrenia needs to be further investigated.
authors.affiliation: Department of Psychology, Institute of Psychiatry, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Boulenguez
authors.forename: S L
authors.initials: SL
authors.lastname: Peters
authors.forename: S N
authors.initials: SN
authors.lastname: Mitchell
authors.forename: J
authors.initials: J
authors.lastname: Chauveau
authors.forename: J A
authors.initials: JA
authors.lastname: Gray
authors.forename: M H
authors.initials: MH
authors.lastname: Joseph
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects*; D012559:Schizophrenia / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D044302:Receptor, Serotonin, 5-HT1B; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D018698:Glutamic Acid; D004298:Dopamine