The present experiment was designed to determine whether disulfiram produced an interoceptive discriminative stimulus (IDS) in rats similar to that exhibited by the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate PTZ (20 mg/kg IP) from saline, according to an FR10 schedule of food reinforcement. After training criteria had been met, discrimination testing revealed that disulfiram (100 mg/kg, IP) produced a PTZ-like IDS that fully substituted for PTZ 4 hours after injection, decaying to baseline values by the third day. The metabolite of disulfiram, diethyl dithiocarbamate (100 mg/kg, IP), followed much the same temporal pattern, but only showed partial substitution for PTZ. When ethanol (1 g/kg, gavage) or the monoamine oxidase inhibitor pargyline (50 mg/kg, IP) were administered in combination with disulfiram, no significant change of the PTZ-like stimulus was observed. Pargyline (100 mg/kg, IP) or acetaldehyde (200 mg/kg, IP), given alone, did not significantly substitute for PTZ. These data show that disulfiram produces an IDS in rats similar to that produced by other anxiogenic drugs. These data also suggest that the mechanism by which disulfiram produces its anxiogenic effect may not be entirely based upon the disulfiram metabolite diethyl dithiocarbamate, elevated acetaldehyde levels or stimulation of the catecholaminergic system.

Acetaldehyde↗

PubMed1993

Cholesterol peroxidation potential as influenced by dietary fat type.

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, influence of two fat vehicles, corn oil (unsaturated) or beef tallow (saturated), on cholesterol induced effects in terms of a) plasma lipoprotein peroxidation and b) aortic accumulation of cholesterol, cholesterol oxide and malonaldehyde was investigated in weanling rabbits. Although the increase in plasma cholesterol induced by cholesterol feeding was similar in both the groups Cu2+ ion induced peroxidation of lipoprotein cholesterol to oxysterols was significantly higher in corn oil group. This difference persisted even at 5 weeks after switching to chow diet. Aortic content of cholesterol and cholesterol oxides was also significantly higher in corn oil group at the end of chow diet period. Aortic accumulation of malonaldehyde (detected by immunocytochemistry) appeared to be greater in corn oil group at the end of the study. These results suggest that fatty acid composition of a given diet during exposure to high dietary cholesterol can influence cholesterol peroxidation to oxysterols and its accumulation in aorta.

Animals↗

PubMed1992