Edward T. Uyeno

Interactions between toluene and alcohol

Weanling male Fischer-344 rats were exposed by inhalation to air or 2000 ppm toluene for 8 hours each day for 2 weeks. Subgroups had access to water or 6% alcohol as their only fluid sources, respectively. Rats exposed to both toluene and alcohol subsequently showed a marked preference for 6% alcohol in two-bottle choice tests that persisted for up to 20 days for some rats. Rats exposed to toluene without access to alcohol and control rats (exposed to air and water) showed a marked aversion to the alcohol solution, and only 2 of 12 rats forced to drink alcohol without exposure to toluene preferred alcohol in the preference tests. Exposure to both toluene and alcohol also caused greater inhibition of weight gain than exposure to either substance alone, accompanied by greater signs of organ toxicity as indicated by clinical blood chemistries. Exposure to toluene caused marked hearing loss as assessed by a behavioral technique (conditioned avoidance), and there was a trend toward enhancement of this ototoxic effect by forced consumption of alcohol.

Alteration of a learned response of the squirrel monkey by hallucinogens

Abstract The relative effectiveness of N,N-dimethyltryptamine derivatives and amphetamine derivatives was evaluated in seven squirrel monkeys, trained to discriminate between two black discs of different sizes. After the animals learned the task, they were injected intraperitoneally with the test compounds and then retested. The dose-response curves showed that debilitating effects of the compounds were a function of dose. The median effective doses ( ED 50 ) that disrupted their performance were calculated according to the graphic logarithmic probit method. The descending rank order of effectiveness of the compounds, according to the ED 50 was: 2,5-dimethoxy-4-ethyl-amphetamine; 2,5-dimethoxy-4-methyl-amphetamine; psilocybin; 4-methoxy-N,N-dimethyltryptamine; N,N-dimethyltryptamine; and 6-hydroxy-N,N-dimethyltryptamine.

Chronic electroshock: Effects on brain weight, brain chemistry, and behavior

Minimum or maximum electroshock convulsions administered chronically to rats resulted in increased brain weight, total brain cholinesterase activity, total protein, and total acetylcholinesterase activity depending upon whether or not full convulsions were induced and on the frequency of their induction over a 17–20 week period. Convulsed rats made more errors in an underwater T-maze than rats given subconvulsive shocks or sham controls.

Structure-activity studies of β-carboline analogs

Abstract A number of β-carboline analogs have been obtained or synthesized, and their in vitro receptor affinities and in vivo antagonist activities determined. The choice of analogs was made in order to explore the importance of the N9-H, the aromatic nitrogen and the C3-ester moiety for high-receptor affinity and antagonist activity of this class of benzodiazepine antagonist. Among the analogs investigated, we describe the properties of 3-cyano-β-carboline ( lh ), the first potent β-carboline antagonist without a carbonyl at the C3-position. The results obtained indicate: (1) Specific interactions of the C3-substituent with key cationic receptor sites rather than electron-withdrawing properties are important for high-receptor affinity and antagonist activity. (2) Specific in-plane interactions of the atomatic nitrogen with a cationic receptor site, rather than stacking with neutral aromatic residues of the receptor are also important for high affinity and antagonist activity. (3) While the presence of an N9H enhances receptor affinity, interaction with an anionic receptor site does not appear essential for antagonist activity.

Substance P found to lower body temperature and aggression

Abstract Synthetic substance P (SP) was bioassayed in mice by a procedure comprising eleven subtests. Two replications of a dose-response study were conducted at the time of the peak effect of the intravenous injection of SP. Single doses of 31 and 63 ng/kg significantly decreased body temperature. SP, [D-Arg1]-SP, and [des-NH2-Arg1]-SP comparably lowered blood pressure, but [D-Arg1]-SP and [des-NH2-Arg1]-SP were 1 20 to 1 10 as active as SP in lowering body temperature. The activities that lower body temperature and blood pressure may be different. The thyrotropin and luteinizing hormone releasing hormones (TRH and LH-RH) did not lower body temperature. SP also decreased the aggressive response (ED50, 89 ng/kg).

Sex and dominance behavior in the rat

Twenty male rats competed against 20 females under survival motivation. In each pair (male vs female) the competitor that forced its opponent back to escape from the underwater tube was considered to be the dominant one of the pair. Nine males and 10 females were dominant, indicating that in the survival competition the males and females do not differ significantly in dominance behavior. The results are in accord with those of Warren & Maroney (1958) who reported that dominance behavior of the rhesus monkey is not related to sex.

Effects ofd-lysergic acid diethylamide and 2-brom-lysergic acid diethylamide on dominance behavior of the rat

Abstract Two dose-response experiments showed that LSD-25 and BOL-148 inhibited dominance behavior in the rats in a food competition situation. Peak effects of LSD-25 and of BOL-148 occurred 15 min and 45 min, respectively, after intraperitoneal injection. The two dose-response curves show that percent inhibition of dominance behavior is an increasing monotonic function of dose. The ED50 shown by LSD-25 and BOL-148 curves are 0.0085 mgkg and 0.75 mgkg, respectively. The much lower ED50 shown by the LSD-25 curve as compared with that of BOL-148 suggests that LSD-25 is a significantly more potent dominance inhibitor than is BOL-148.

Selective effect on punished versus unpunished responding in a conflict as the criterion for anxiogenic activity

The punished drinking test has been used successfully for identifying and studying anxiolytic agents. By reducing the level of punishment (i.e., decreasing the intensity of shock), it has also been used as a method for measuring anxiogenic activity. Because anxiogenic behavior is a novel and important concept that is not yet fully established, we have reinvestigated the effects of two putative inverse benzodiazepine agonists and pentylenetetrazol in this conflict test. In a series of experiments, using both our version of the procedure and a replication of a previously published method, we were unable to demonstrate a selective reduction in punished responding over unpunished responding caused by CGS 8216 (3 to 40 mg/kg), FG 7142 (2 to 6 mg/kg), and pentylenetetrazol (10 to 20 mg/kg) as reported previously. A careful comparison of the details of our method and the published procedure failed to reveal the source of this discrepancy. If anxiogenic behavior is to be defined as a selective effect of a drug on punished response, the value of this test will depend on identification of its critical variables.

Relative potency of amphetamine derivatives and N,N-dimethyltryptamines

The relative potency of amphetamine derivatives and N,N-dimethyltryptamine (DMT) derivatives was evaluated in rats trained to swim through an underwater tube in order to escape at the other and of the tank. All of the compounds tested significantly increased the starting latency. The time of peak effect of 2,5-dimethoxy-4-ethyl-amphetamine (DOET), 2,5-dimethoxy-4-methyl-amphetamine (DOM), and 6-hydroxy-DMT was estimated at 40 min after the intraperitoneal injection and that of DMT, 4-methoxy-DMT, and psilocybin was 20 min. Dose-response curves showed that the increase in the latency was dose-dependent. The descending rank order of potency of the compounds, according to the median effective dose (ED50), was: DOET, psilocybin, DOM, DMT, 4-methoxy-DMT, and 6-hydroxy-DMT.

Lysergic acid diethylamide and a novel stimulus

The mean running time of rats injected with 0.016 mg/kg of lysergic acid diethylamide (LSD-25) was not significantly different from that of others, administered saline solution. However, when a novel stimulus (hurdle) was presented in the runway, the mean running time of the experimental group was significantly longer than that of the control group.