Perkinsus marinus tissue distribution and seasonal variation in oysters Crassostrea virginica from Florida, Virginia and New York.

Perkinsus marinus infection intensity was measured in eastern oysters Crassostrea virginica collected in October and December 1993, and March, May, and July 1994 from 3 U.S. sites: Apalachicola Bay (FL), Chesapeake Bay (VA), and Oyster Bay (NY). Gill, mantle, digestive gland, adductor muscle, hemolymph, and remaining tissue (including gonadal material and rectum) were dissected from 20 oysters from each site at each collection time. Samples were separately diagnosed for P. marinus infections by incubation in Ray's Fluid Thioglycollate Medium (RFTM) and subsequent microscopic quantification of purified enlarged hypnospores. At all sampling times and sites, average P. marinus infection intensity (g wet wt tissue-1 or ml hemolymph-1) was lowest in hemolymph samples, and generally highest in the digestive gland. Perkinsus marinus prevalence was 100% at both FL and NY sites for each of the 5 collection times, and, for the VA site, was less than 100% in only 1 month (May 1994). Seasonal intensity patterns and mean total body burdens differed among the sites. Average body burden was highest in VA during October and progressively declined to a minimum in May. This decline was probably due to mortality of heavily infected oysters and diminution of parasite activity associated with colder temperatures and reduced salinities. Intensities varied little during the months of October and December at both the FL and NY sites. Minimum average intensities were observed in March in FL oysters and May in NY oysters. Relatively high P. marinus infection levels that persisted throughout the winter in NY oysters compared with VA oysters could reflect constant high salinity in Long Island Sound which favors parasite activity, and also rapid decline in temperature in the fall that may have prevented epizootic oyster mortalities.

Seroquel: electrophysiological profile of a potential atypical antipsychotic.

Extracellular single unit recording techniques were employed to compare the effects of seroquel with the reference antipsychotic (AP) agents clozapine and haloperidol in electrophysiological tests that may predict AP activity. Seroquel and clozapine were differentially more active in reversing the inhibitory actions of d-amphetamine on mesolimbic (A10) than nigrostriatal (A9) dopamine (DA)-containing neurons, whereas haloperidol exhibited the opposite selectivity. In cell population studies, acute treatment with seroquel and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells following repeated (28 day) administration. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after repeated treatment. Since DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects (EPS) and tardive dyskinesia (TD), seroquel, like clozapine, may be an atypical AP with a reduced likelihood for producing EPS/TD.

Effects of ICI 169,369, a selective serotonin2 antagonist, in electrophysiological tests predictive of antipsychotic activity.

Extracellular single unit recording techniques were used to compare the effects of ICI 169,369, a selective serotonin2 receptor antagonist, with the reference antipsychotic (AP) agents clozapine and haloperidol, in electrophysiological tests that may predict AP activity. ICI 169,369 was found to reverse the inhibitory actions of amphetamine on A9 and A10 dopamine (DA) neurons, a common property shared by other AP drugs, and was comparable in potency to clozapine. In cell population studies, acute treatment with ICI 169,369 (at a low dose only) and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells after chronic administration. Interestingly, chronic treatment with ICI 169,369 also caused a significant increase in the number of actively discharging A9 DA cells, an effect not predicted on the basis of the acute data. A similar effect was noted for clozapine, although the magnitude did not reach statistical significance. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after chronic treatment. Inasmuch as DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects, ICI 169,369, like clozapine, may be a potential AP with a reduced likelihood for producing extrapyramidal side effects.

D-2 dopamine antagonist-like effects of SCH 23390 on A9 and A10 dopamine neurons.

The effects of SCH 23390 on d-amphetamine-induced suppression of A9 and A10 DA neuronal firing were determined. SCH 23390 potently reversed d-amphetamine on both A9 and A10 DA neurons. Compared to haloperidol, SCH 23390 was 5 times more potent on A9 DA neurons and 20 times more potent on A10 DA neurons. However, the magnitude of the reversal effect was greater with haloperidol than SCH 23390. In addition, haloperidol produced a further increase in firing of both A9 and A10 DA neurons after SCH 23390 maximally increased firing. It was concluded that SCH 23390 has D-2 DA antagonist-like properties, possibly mediated via an interaction at D-1 DA receptors, which may be functionally linked with D-2 DA receptors. The marked potency of SCH 23390 in reversing d-amphetamine could be due to its combined antagonist effects at 5HT2 and D-1 DA receptor sites.

Interactions of Ro 15-1788, CGS 8216 and diazepam on head-turning in rats.

Ro 15-1788 (10 mg/kg, ip) and CGS 8216 (10 mg/kg, ip) significantly reversed the inhibitory effect of diazepam (5 mg/kg, ip) on electrically induced head-turning in rats. Neither antagonist alone, at the dose level which blocked diazepam, had any intrinsic activity in this model. The specificity of the interaction between CGS 8216 and diazepam was further confirmed by the lack of antagonism by CGS 8216 of muscimol's inhibitory effect on head-turning. These results provide additional evidence that the inhibition of head-turning induced by diazepam is mediated via the benzodiazepine binding site. Furthermore, this model provides a functional expression of the interaction between the benzodiazepine recognition site, the chloride ionophore, and the GABA receptor complex.