These results are discussed with respect to the potential use and safety of kappa agonists for clinical indications.

This study provides empirical evidence for the commonly accepted belief that the abuse liability of cocaine can be enhanced by increasing the rate of the intravenous infusion; this principal may not hold true for opioids but further work would be required to rule this out. The data also indicate that moderate doses of cocaine can be administered over a range of infusion speeds commonly used in experimental settings without appreciably altering the apparent medical risks.

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A number of chemically distinct anxiolytics were examined for effects on defensive behavior (foot-shock-induced freezing) in rats. Central nervous system acting drugs which are not anxiolytics were also studied. Animals were injected with a drug or vehicle (IP) prior to being placed in a chamber with a grid floor through which two footshocks were delivered. Behavior was observed during the pre-shock period (2 min) and for 4 min after the second footshock. The effects of the following drugs on the duration of footshock-induced freezing were studied: diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic acid (NPC 12626); 3-((+/-)-2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP); [(+)-5-methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10- imine (MK-801); buspirone hydrochloride (BUS); DL-amphetamine sulfate (AMP); haloperidol (HAL); ethyl-beta-carboline-3 carboxylate (beta-CCE). Compounds which reduced the duration of footshock-induced freezing included DZP, BUS, and the competitive NMDA antagonists NPC 12626 and CPP. The non-competitive NMDA antagonist, MK-801, had no effect on the response. The highest dose of amphetamine tested also reduced footshock-induced freezing. However, amphetamine-treated animals did not locomote or rear after footshock, suggesting fear of the environment. Animals injected with DZP, NPC 12626, CPP or buspirone spent at least 1.4 of the 4 post shock minutes locomoting. Haloperidol had no effect on freezing at the doses tested. beta-CCE tended to increase the duration of footshock-induced freezing.(ABSTRACT TRUNCATED AT 250 WORDS)

Unpublished observations suggested that some subjects in human drug discrimination studies acquired a drug versus placebo discrimination by tasting the capsule contents. To evaluate the prevalence of this behavior and to develop approaches to circumvent this problem, 30 normal human subjects participated in a drug discrimination study in which the study capsules (i.e., lactose and lactose + quinine) could be discriminated by tasting the capsule contents but were otherwise pharmacologically indistinguishable. Twenty percent of the subjects significantly discriminated between the capsules; this discrimination was disrupted by employing thorough mouth checks following capsule administration. Based on these findings, we recommend that human drug discrimination studies incorporate procedures that minimize the possibility of drug tasting by requiring consumption of sufficient fluid in combination with rigorous mouth checks to ensure capsule swallowing.

We observed a high incidence of several ocular manifestations in the acute phase of leptospirosis. Despite the systemic severity and high incidence of ocular disorders in the acute phase of leptospirosis, the short-term visual outcome of these patients was good.

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