Biomedical subjects

R S Lewis

Publications and source records attributed to R S Lewis.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Specific decreases in ethanol- but not water-reinforced responding produced by the 5-HT3 antagonist ICS 205-930.

The serotonin 5-HT3 antagonist ICS 205-930 has been shown to block the discriminative stimulus properties of ethanol and decrease voluntary intake, suggesting a possible role for 5-HT3 systems in the reinforcing effects of ethanol. ICS 205-930 (0.56, 1.0, 3.0, 10.0, and 17.0 mg/kg i.p.) was examined on ethanol and water self-administration in an operant paradigm. Following a sucrose-fading procedure, two groups of nondeprived rats responded on either a concurrent fixed ratio 4 schedule for ethanol (10% v/v) and water (CONC FR4 FR4), or a single FR4 schedule for ethanol (10% v/v). ICS 205-930 dose-dependently decreased ethanol-reinforced responding in the concurrent condition without decreasing water-reinforced responding, suggesting a specific effect on ethanol. Ethanol-reinforced responding was also dose-dependently decreased in the single FR4 condition, but the dose effect curve was shifted to the left. These data support the conclusions that 5-HT3 systems may play a specific role in ethanol self-administration that is independent of general appetitive and motor processes, and that 5-HT3 antagonists may have therapeutic efficacy in the treatment of alcohol abuse when multiple reinforcers are available.

Alcohol Drinking↗

PubMedDate not supplied

Ethanol self-administration by alcohol-nonpreferring (NP) rats in a continuous access situation.

Male rats, from the alcohol nonpreferring (NP) line, were studied in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 h/d. The NP rats consumed less ethanol per day following 7 weeks under these conditions than did either alcohol-preferring (P) rats or Long-Evans (LE) studied previously under the same conditions for 4 weeks. The NP rats consumed 0.2 g/kg per day during the first week of the experiment, 0.72 g/kg per day during the fourth week, and 1.03 g/kg per day during the seventh week compared to 2.2 g/kg per day for LE rats and 4.8 g/kg per day for P rats following 4 weeks. These data indicate that NP rats will slowly initiate ethanol self-administration under continuous access conditions, but to a lesser extent and at a slower rate than other lines of rats studied previously.

Alcoholism↗

PubMedDate not supplied

Effects of continuous versus limited access to ethanol on ethanol self-administration.

Eight male, experimentally naive Long-Evans rats were housed in operant chambers 23 h per day following initiation to self-administer ethanol. While housed in the chambers, the animals had continuous access to food pellets according to a fixed ratio 1 schedule of reinforcement, 10% ethanol (v/v) according to a fixed ratio 4 schedule of reinforcement and water in a drinking tube with licks recorded via a drinkometer. Over a series of experimental phases, daily availability of the ethanol solution was limited to 16, 6, 4, 2, or 1 30-min period per day. The 1 30-min period access was examined during the 12th hour or the second hour of the daily sessions. Over the course of the experiment, total responses on the lever that operated the dipper, g/kg per day and number of ethanol drinking bouts per day decreased significantly as the number of daily access periods decreased. On the other hand, the number of dippers presented per ethanol bout, g/kg per ethanol bout and ethanol bout duration increased, with significant increases in dippers per bout occurring when one 30-min access period per day was provided. These data indicate that the size of a single ethanol drinking bout can be increased somewhat by limiting the opportunity to obtain ethanol reinforcement and agrees with earlier research that has shown similar effects.

Animals↗

PubMedDate not supplied

The influence of delivery rate on the chemistry and biological effects of nitric oxide.

Nitric oxide can be introduced slowly and steadily into aqueous solutions, including cell culture media, over extended periods of time via semipermeable Silastic (a registered trademark of the Dow Corning Corp.) polymer membranes. The rates of introduction are predictable and reproducible and can approach rates of nitric oxide production by stimulated cells, such as macrophages, that express inducible nitric oxide synthases. DNA damage in Chinese hamster ovary cells by membrane-delivered nitric oxide is comparable to that observed in the DNA of stimulated macrophages. Toxicity and mutagenicity of nitric oxide toward Salmonella typhimurium, toxicity of nitric oxide toward Chinese hamster ovary cells, and nitrosation of dimethylmorpholine are all more efficient when nitric oxide is delivered by membrane than when an equivalent amount of gaseous nitric oxide is added by syringe.

Animals↗

PubMedDate not supplied

Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions.

An understanding of the rate of reaction of nitric oxide (NO) with oxygen in aqueous solutions is needed in assessing the various actions of NO in the body. A novel approach was developed for studying the kinetics of this reaction, which permitted simultaneous and continuous measurements of the concentrations of NO and the principal product, nitrite (NO2-). Nitric oxide was measured using a chemiluminescence detector, with continuous sampling achieved by diffusion of NO through a membrane fitted into the base of a small, stirred reactor. The results with various initial NO and O2 concentrations confirmed that the rate of reaction is second-order in NO and first-order in O2. The rate of reaction of NO was described by the expression 4k1 [NO]2[O2], where k1 was (2.1 +/- 0.4) x 10(6) M-2 s-1 at 23 degrees C and (2.4 +/- 0.3) x 10(6) M-2 s-1 at 37 degrees C. The value of k1 was the same at pH 4.9 and 7.4. The rate of formation of NO2- equaled the rate of reaction of NO (within experimental uncertainty of a few percent), and there was no detectable formation of nitrate (NO3-). This confirmed that NO and NO2- were the only NOx species present in significant amounts and supported the validity of pseudo-steady-state assumptions for NO2 and N2O3, which are intermediates in the conversion of NO to NO2-.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics↗

PubMedDate not supplied

Voltage- and ion-dependent conductances in solitary vertebrate hair cells.

An important function of the peripheral auditory system is the resolution of complex sounds into their constituent frequency components. It is well established that each mechanoreceptive hair cell of the cochlea is maximally sensitive to a particular frequency of sound, but the mechanisms by which this sharp frequency selectivity is achieved are still controversial. The complex mechanical and hydrodynamic properties of the receptor organs and of the hair cells themselves are certainly involved. However, in at least one auditory organ, the turtle cochlea, frequency tuning is greatly enhanced by the electrical properties of the hair-cell membrane; each cell in this organ behaves as an electrical resonator tuned to a narrow band of frequencies. Using the 'Gigaseal', whole-cell recording technique, we have investigated the biophysical basis of similar resonant behaviour in enzymatically isolated hair cells from the bullfrog sacculus. We report here the identification of three voltage- and ion-dependent conductances which may contribute to the electrical tuning mechanism: a non-inactivating calcium conductance, an A-type K+ conductance, and a Ca2+-activated K+ conductance.

Animals↗

PubMedDate not supplied

Design of a novel apparatus to study nitric oxide (NO) inhibition of platelet adhesion.

Nitric oxide (NO) is a simple biological molecule which inhibits adhesion and aggregation of platelets. A novel NO delivery device has been developed to quantitatively study the effects of NO concentration and flux on the adhesion of platelets to a surface. The slit-flow device is lined with a protein-coated membrane through which NO gas permeates into a perfusing platelet suspension. A model predicting spatial NO concentrations and fluxes within the flow slit was validated. At a wall shear rate of 250 s(-1), platelet adhesion was inhibited 87% relative to controls for exposures as low as 0.1 ppm NO. Corresponding model predictions of the aqueous NO concentration and fluxes at the surface were 0.15 nM, and between 0.5 and 1.1 nanomoles cm(-2) s(-1), respectively. Endothelial cells, which release NO to inhibit platelet adhesion in vivo, generate NO at an estimated flux similar to the above values. At a NO exposure of 0.02 ppm, platelet inhibition was only 10%. The delivery device is useful for other studies in which a knowledge of the spatial NO fluxes or concentrations is desired. Knowledge of these fluxes or concentrations is beneficial towards the design of biomaterials incorporating NO to inhibit platelet adhesion.

Biomedical Engineering↗