Psychopharmacology communications最新文献

In a comparative study, the effective of intraventricularly or intraperitoneally injected p-chloroamphetamine (p-CA) and some chloroindoles on cerebral levels of serotonin was evaluated. 5-Chloroindole depressed 5-HT levels in the brainstem and telencephalon for three days, 6-chloro-2-methylindole (6-CMI) only during the first day. 5-Chloroindazole had no effect at all. p-CA was more toxic to guinea pigs than to rats. p-CA and 5-chloro-2-methylindole (5-CMI) had no effect on cerebral 5-HT in chicks. Apparently, none of these compounds represented or was converted to a metabolite possibly responsible for the neurotoxic effects of p-CA.

The relative potency of dopaminergic inhibition and serotonergic stimulation of prolactin secretion in male rats was compared. 5-Hydroxytryptophan (5-HTP), 100 mg/kg, i.p., the precursor of serotonin, produced a 6-11 fold increase in plasma prolactin. Apomorphine, a dopamine agonist, at doses of 1-10 mg/kg, i.p., had no significant effect on plasma prolactin. However, when apomorphine was given with or before 5-HTP, it nearly completely blocked the increase in prolactin produced by 5-htp. these results indicate that inhibition of prolactin secretion by dopaminergic stimulation can overcome the prolactin releasing effect of serotonin. The results are consistent with the hypothesis that prolactin secretion is ordinarily under a weak serotonergic stimulation and a profound dopaminergic inhibition. It is also possible that apomorphine affects plasma prolactin levels by increasing prolactin clearance.

Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia.

The effects of biogenic amines on adenylate cyclase from rhesus monkey brain have been surveyed. Dopamine-responsive cyclase activity was found throughout the subcortical limbic area and limbic cortex, as well as in the sensorimotor cortex, where stimulation by dopamine was blocked by fluphenazine. Cyclase activity from caudate nucleus in rat and rhesus monkey was very similar in relative responsiveness to stimulation by dopamine and norepinephrine. Some response of the enzyme from cingulate and sensorimotor cortex to isoproterenol was observed. The inhibition by fluphenazine of dopamine-responsive cyclase activity from sensorimotor cortex raises the possibility of a cerebrocortical locus of action for antipsychotic agents.

The effects of the intravenous administration of cocaine (0.05-5.0 mg/kg) on body temperature, heart rate, respiration rate and several unconditioned behavioral categories were ascertained in unanesthetized male rhesus monkeys. Statistically significant increases in body temperature, respiration rate and heart rate occurred only after the largest dosage tested. Subjective increases in pupil size, activity, reactivity and vocalization as well as the occurrence of stereotyped behaviors, mydriasis and refusal to ingest fruit, were observed following injection with 0.2, 0.5 mg/kg and 5.0 mg/kg. A large degree of consistent intersubject variability in the magnitude of these responses was present. There was no consistent correlation across subjects between the magnitude of these responses and the plasma level of cocaine. However, within a given subject a direct correlation existed between these parameters.

It has been found that in the brain of the non-human primate (Macaca arctoides) MHPG occurs principally if not exclusively in the free rather than the conjugated form. It has also been found that in all areas of human brain examined MHPG is present in the free form rather than the conjugated form. The quantity of free MHPG present in various structures of human brain ranged from 46.4 to 69.8 microng/gm of tissue.

Reserpine (1 mg/kg) was administered to pregnant rats on days 12, 13 and 14 of gestation. Although adrenal tyrosine hydroxylase and dopamine beta-hydroxylase activities were normal in the offspring at 4 days of postnatal age, both were elevated by 17 days and the elevations persisted into adulthood. The changes may result from permanently increased sympatho-adrenal stimulation.

In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect.

This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising.