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

Microinjection of a serotonergic 5-HT1B agonist (S-CM-GTNH(2), 3 mu g/ l) into-the dorsal subiculum (DS) induced long-lasting increases in do pamine (DA; +58%), dihydroxyphenylacetic acid (DOPAC; +15%) and homova nillic 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 a ccumbens (n. acc). Perfusion of a glutamate-N-methyl-D-aspartate (NMDA ) receptor antagonist (MK 801, dizocilpine, 10 mu M) through the dialy sis probe in the n. acc induced similar long-lasting increases in DA a nd DOPAC, whereas the glutamate-quisqualate/kainate receptor antagonis t (CNQX, 50 mu M) had no effect. In the presence of dizocilpine in the n. acc, microinjection of S-CM-GTNH(2) into the DS could still increa se DOPAC and HVA, but DA levels were not further changed, whereas in t he presence of CNQX, microinjection of S-CM-GTNH(2) 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 t he n. acc, presumably via the glutamatergic projection to this structu re and acting through NMDA receptors in it. This implies either the su ppression of a tonic indirect inhibitory influence and/or stimulation of a phasic excitatory effect of glutamate. Disruption of latent inhib ition (LI) has been suggested as a model for a cognitive deficit in sc hizophrenia (hyperattention to irrelevant stimuli) and is usually asso ciated with an increase in DA release in the n. acc. However, s.c. inj ection 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 unc hanged. 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 releas e in the n. acc are functionally equivalent. Sensitization of receptor s or impulse-dependent increase in DA release might be necessary to di srupt LI. The possible role of altered serotonergic transmission, thro ugh h5-HT1B receptors (human homologue of the rat 5-HT1B receptors) lo cated in the DS, in acute schizophrenia needs to be further investigat ed.