High-affinity benzodiazepine antagonists reduce responding maintained by ethanol presentation in ethanol-preferring rats.

In the present study, we examined two high-affinity and selective benzodiazepine (BDZ) receptor antagonists (ZK 93426, CGS 8216) in ethanol (EtOH)-preferring rats whose responding (i.e., lever pressing) was maintained by the presentation of EtOH. The in vivo actions of CGS 8216 (1-30 mg/kg) and ZK 93426 (5-75 mg/kg) were examined after intraperitoneal or oral administration. Flumazenil (10-40 mg/kg) was used as a reference BDZ antagonist. EtOH (10% v/v) and saccharin (0.05 g/v) solutions were concurrently available for 30 min each day under a two-lever fixed-ratio schedule in which four responses on one lever produced the EtOH solution and four responses on the other lever produced the saccharin solution. A 40 mg/kg intraperitoneal injection of flumazenil given on the first injection day (day 1) nonsignificantly reduced control levels of responding maintained by EtOH by 36%. No effects were observed 24 hr after drug administration (day 2). Oral administration of flumazenil was without effect. On day 1, intraperitoneal administration of CGS 8216 (1-20 mg/kg) and ZK 93426 (1-50 mg/kg) reduced control levels of responding maintained by EtOH by 44% to 73%; on day 2, EtOH maintained responding continued to be suppressed with the highest doses (> or = 20 mg/kg) suppressing control levels of responding by as much as 62%. Oral administration of higher doses of CGS 8216 (5-30 mg/kg) and ZK 93426 (10-75 mg/kg) reduced responding maintained by EtOH by as much as 54% to 84% of controls; however, no effects were seen on day 2. Only the highest intraperitoneal dose of ZK 93426 (50 mg/kg) suppressed responding maintained by saccharin. These findings demonstrate that some BDZ antagonists decrease responding maintained by EtOH. The findings suggest that certain BDZ antagonists may have potential as pharmacotherapies to prevent or decrease EtOH abuse in humans.

Synthesis of linoleate and alpha-linolenate by chain elongation in the rat.

The objective was to determine whether rats could synthesize longer chain polyunsaturates from hexadecadienoate (16:2n-6) and hexadecatrienoate (16:3n-3). Rats were gavaged with uniformly 13C-labelled hexadecadienoate or hexadecatrienoate, euthanized 24 h later, and total lipids were extracted from liver and carcass. Gas chromatography/combustion/isotope ratio mass spectrometry was used to measure 13C levels in individual liver, carcass, and whole body fatty acids. 13C Enrichment was present in desaturated and chain-elongated polyunsaturates, including linoleate, arachidonate, alpha-linolenate, and docosahexaenoate at 12-13% of the dose of tracer given. 13C Enrichment from hexadecatrienoate was highest in carcass and liver alpha-linolenate, representing 3.5 and 17.9% of the total alpha-linolenate pool, respectively. For linoleate, arachidonate, or docosahexaenoate, the contribution of 13C did not exceed 0.2% of the total body pool. Green leafy vegetables common in the human diet were shown to contain up to 1.2% of total fatty acids as hexadecadienoate and 11.6% as hexadecatrienoate. Hence, humans consuming green vegetables probably synthesize a small proportion of their total body content of linoleate and alpha-linolenate.

Dissolved hydrocarbons and related microflora in a fjordal seaport: sources, sinks, concentrations, and kinetics.

The continuous addition of toluene as a solute of treated ballast water from oil tankers into a well-defined estuary facilitated the study of the dynamics of dissolved hydrocarbon metabolism in seawater. Most rates of toluene oxidation were in the range of 1 to 30 pg/liter per h at 0.5 mug of toluene per liter. Near the ballast water injection point, a layer of warm ballast water, rich in bacteria, that was trapped below the less-dense fresh surface water was located. Toluene residence times were approximately 2 weeks in this layer, 2 years elsewhere in Port Valdez, and 2 decades in the surface water of a more oceanic receiving estuary adjacent. Mixing was adequate for a steady-state treatment which showed that 98% of the toluene was flushed from Port Valdez before metabolism and gave a steady-state concentration of 0.18 mug/liter. Total bacterial biomass from direct counts and organism size data was usually near 0.1 mg/liter, but ranged up to 0.8 mg/liter in the bacteria-rich layer. The origin of bacteria in this layer was traced to growth in oil tanker ballast during shipments. The biomass of toluene oxidizers in water samples was estimated from the average affinity of pure-culture isolates for toluene (28 liters per g of cells per h) and observed toluene oxidation kinetics. Values ranged from nearly all of the total bacterial biomass within the bacteria-rich layer down to 0.2% at points far removed. Because the population of toluene oxidizers was large with respect to the amount of toluene consumed and because water from a nearby nonpolluted estuary was equally active in facilitating toluene metabolism, we searched for an additional hydrocarbon source. It was found that terpenes could be washed from spruce trees by simulated rainfall, which suggested that riparian conifers provide an additional and significant hydrocarbon source to seawater.