Psychopharmacology communications最新文献

2-Dimethylaminoethanol and acetylcholine were iontophoretically tested on deep, spontaneously firing, neurons of the rat cerebral cortex. All identified corticospinal cells and 71% of the unidentified ones were excited by Deanol. Eight percent of the latter group were inhibited. All but one neuron responded similarly to ACh and Deanol, when both substances were tested on the same neuron. Atropine reversibly blocked these responses. The implications of these observations are discussed with regard to cholinergic synapses in the brain and the rationalization of the therapeutic use of Deanol.

7,8-Dihydroxychlorpromazine 7,8-diOH-CPZ) is known to undergo auto-oxidation when exposed to air. Hydrogen peroxide is formed during this process, and the amount formed can be calculated from the amount of oxygen produced upon the addition of catalase. In the presence of superoxide dismutase the rate of oxidation of the CPZ metabolite is accelerated, accompanied by an increased production of hydrogen peroxide. When similar incubation are carried out with rat brain mitochondria present, hydrogen peroxide production is no longer detectable. The implications of this finding with regard to in vivo hydrogen peroxide production during the auto-oxidation of 7,8-diOH-CPZ are discussed. A preliminary report has been presented (1).

Lumbar cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) following probenecid was negatively correlated with prognostic variables in a group of schizophrenic patients. Acute schizophrenic patients had lower CSF 5HIIA was negatively correlated with measured activity and rated agitation in a mixed group of schizophrenic patients. There is compelling evidence that LSD directly inhibits the firing of serotonergic neurons. Individuals who developed prolonged psychotic reactions following LSD ingestion had relatively good premorbid trait histories and a family history of psychosis in 33% of cases compared to 21% for non drug-induced psychotic patients. If central serotonin system in man are mainly inhibitory, our results are consistent with the hypothesis that in some acute psychotic states a primary decreases in sertonergic neuronal activity may contribute to excessive central nervous system arousal.

Rats administered chronic haloperidol (5 mg/cc) for 2 months exhibited stereotyped gnawing during chronic haloperidol treatment, and after withdrawal from haloperidol, showed significantly greater stereotyped behavior induced by apomorphine or L-amphetamine compared to saline controls. Chronic administration of benztropine mesylate concomitantly with haloperidol reduced the effects of chronic haloperidol on drug induced stereotyped behavior during the withdrawal period.

It has been proposed that the etiologies of tardive dyskinesia and Huntington's chorea and of some forms of schizophrenia and the affective disorders involve a cholinergic imbalance with respect to a second neurotransmitter. This relative over- or underactivity of the cholinergic system could result from altered synthesis, storage, release, degradation, or reuptake or from a variety of receptor interactions. Under these hypotheses, clinical symptoms would reflect both the brain region in which the imbalance occurs and the neurotransmitter with which acetylcholine is interacting. Effective treatments could involve the correction of this hypothetical imbalance by changing the relative availability of either one or both of the neurotransmitters. Both precursor loading with choline or dimethylaminoethanol and cholinesterase inhibition may be useful in evaluating the effects of increased cholinergic activity in these disease states; the relative merits of these strategies are discussed.

Previous work has demonstrated that thyrotropin-releasing hormone (TRH) and its beta-alanine analogue (beta-ala TRH) are potent antagonists of barbiturate-induced sedation. This study sought to determine the effects of these oligopeptides on the anticonvulsant properties of phenobarbital in the maximal electroshock seizure (MES) test. Pro-leu-gly-NH2, another hypothalmic peptide was also examined. None of the peptides studied had any anticonvulsant properties of their own, but TRH and beta-ala TRH, though not pro-leu-gly-NH2, potentiated the anticonvulsant potency of phenobarbital. Thyrotropin (TSH) and tri-iodothyronine (T3) were in effective, suggesting that the effects observed with TRH are not mediated via the pituitary-thyroid axis. Since phenobarbital treatment of grand mal epilepsy is often limited by sedation and since TRH antogonizes sedation and enhances anticonvulsant effects of the barbiturate, the hormone or a congener may find value as an adjunct in therapy.

The emergence of specific concepts of possible neuronal pathophysiology in mental disorders has recently been accelerated by the realization that the central catecholamine and indoleamine pathways show potent and widespread actions in animal experiments. These functional properties have been characterized in part by new methods of neuronal circuit analysis, more specific methods of neuronal cytochemistry, and by extensive exploitation of more classical electrophysiological methodologies for the assessment of synaptic transmitter identification and mechanism, the results of experiments at the cellular level have permitted additional studies to be done on the possible behavioral significance of the events regulated by monamines in the awake animal, When the cytochemical and electrophysiological and behavioral exeriments are considered as connected aspects of the same brain sub-systems, then the simple electrophysiological concepts of excitation and inhibition seem inadequate to explain the integrative, amplifying and biochemical actions which can be performed by experimental manipulation of central monamine pathways.

Tryptophan hydroxylase activity rises rapidly after birth in 5 distinct regions of the rat CNS. Near-adult levels of activity are recorded by 22 days of age in the cell-body rich regions of the brainstem and by 42 days in the terminal-rich areas, hypothalamus and remaining forebrain. The intracisternal injection of 40 mug 5,7-dihydroxytryptamine on day 2 after birth results in a near-total depletion of tryptophan hydroxylase in all CNS regions analyzed 6 or 12 days after drug administration. Enzyme activity recovers (to 11-24% of age matched controls) between day 12 and 20 after 5,7-dihydroxytryptamine in hypothalamus, midbrain and pons medulla oblongata. The growth of 5,7-DHT-treated animals is retarded between 3 and 40 days after drug administration.

The water intake of rats was observed following subcutaneous administration of intra and extracellular thirst stimuli (hypertonic saline, polyethylene glycol, angiotensin, and isoproterenol) before and after chronic treatment with the anticholinesterase agent, diisopropyl fluorophosphate (DFP), and its arachis oil vehicle. Only hypertonic saline and isoproterenol reliably increased water intake in both groups prior to chronic treatment. After chronic treatment hypertonic saline produced the same degree of water intake in the DFP-treated and control animals, but isoproterenol appeared to produce a greater degree of water intake in the DFP-treated than in the control rats. These results suggest that there are no gross disturbances in the mechanisms underlying intra and extracellular thirst stimuli following the development of tolerance to DFP.

The correlation between chlorpromazine (CPZ) levels in rat brain and serum with hypothermia was investigated. Even large differences between brain and serum concentrations of CPZ could be demonstrated at the two dosages of the drug investigated, the groups showed an identical hypothermic effect between 5 to 30 minutes, with maximum hypothermia being reached 1 hour. It also appears that when brain concentrations of CPZ were lower than 1 mug/g, body temperature returned to normal. We could not demonstrate any preferential uptake of CPZ into the hypothalamus, the proposed site at which CPZ acts to cause hypothermia.