Sex differences of the content on the monoamines levels in symmetrical structures of the C3H-A mice brain

The Sex differenses in the content and metabolism of dopamine and serotonin were studied in symmetrical brain structures of C3H-A mice. With HPLC the contents of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites, such as dihydroxyphenylacetic acid (DOPAC), homovanillinic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA), were measured in the cortex, tuberculum olfactorium, hippocampus and striatum of both the right and the left hemispheres of the brain in male and female mice. The following sex differences in monoamines and their metabolites in brain areas were found: the NE content was higher in the male striatum and in the female tuberculum olfactorium; in males the DA content in cortex and hippocampus was higher, but in tuberculum olfactorium and striatum was lower than that in females; in females the 5-HT and 5-HIAA levels in hippocampus and tuberculum olfactorium were hither than that in males. In the female left striatum the 5-HIAA content was higher than in males. In males three cases of neurochemical cerebral hemisphere asymmetries were found: 1) the NE content is higher in the right tuberculum olfactorium, 2) the DA level is higher in the right hippocampus, 3) the 5-HIAA content is higher in the left hippocampus. In females the only one case of cerebral asymmetry was found, i. g. the 5-HT level was higher in the right tuberculum olfactorium.

Subcortical limbic 3H-N-propylnorapomorphine binding sites are markedly modulated by cholecystokinin-8 in vitro

By means of the dopamine (DA) agonist radio ligand 3H-N-propyinorapomorphine (3H-NPA) the effects of cholecystokinin-8 (CCK-8) have been evaluated in vitro on the binding characteristics of the DA agonist sites in membrane preparations from the subcortical limbic forebrain containing mainly nucleus accumbens and tuberculum olfactorium. It was shown that CCK-8 (10−8 M) can produce a 40% increase in the KD value of the 3H-NPA binding sites and a significant I0% increase in the Bmax values of these sites. It is therefore suggested that there exist marked receptor-receptor interactions between the CCK-8 binding sites and DA agonist binding sites in the limbic forebrain. On the basis of these findings and in view of the fact that CCK peptides are comodulators in certain types of mesolimbic DNA neurons but cannot modulate DA release in these DNA synapses) the hypothesis is introduced that the presence of DA comodulators such as CCK-8 in the DA synapses makes possible a heterostatic regulation of the synapse. Thus, by means of receptor-receptor interactions, peptide comodulators may change the set point of the main transmission line without inducing homeostatic feedback responses on synthesis and release of the main transmitter, opening up a new way to modulate chemical transmission in general.

The coincidence of schizophrenia and Parkinsonism: some neurochemical implications

SynopsisThe hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the pathophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as.postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-striatal sites.