Comparative effects of chronic administration of some psychotropic drugs on rat brain cortex acetylcholinesterase activity.

The response of central cholinergic neurotransmission to the chronic administration of some psychotropic drugs to rats was investigated using brain acetylcholinesterase activity as a neurochemical marker for cholinergic neurons. Rats were divided into four groups. Three experimental groups were given chlorpromazine, amitriptyline, or diazepam respectively, for a period of 30 days; and the control group received physiological saline only. Long-term treatment of chlorpromazine and amitriptyline resulted in significant increases in rat brain cortex enzyme activity, whereas only a slight increase was observed in the diazepam-treated group. These results indicate that the chronic treatment with some psychotropic drugs causes changes in central cholinergic transmission.

Liver delta-aminolevulinate dehydratase activity in amitriptyline- or chlorpromazine-treated rats.

Amitriptyline (AMT) and chlorpromazine (CPZ) (0.5 mg per animal, i.p.) were injected into rats separately for 30 days and their effects on heme metabolism in liver were examined. Significant decreases in the delta-aminolevulinate dehydratase activity were observed following the administration of both drugs (mean value of AMT-group: 6.58 U/g tissue; and CPZ-group: 7.04 U/g tissue) in comparison to that of controls (11.71 U/g tissue); however total liver heme content was not altered. When 24-h urinary excretions of delta-aminolevulinate (ALA) and porphobilinogen (PBG) were measured on the last day of the experiment, a slight (AMT-group: 38.40 micrograms/day) to distinct (CPZ-group: 59.11 micrograms/day) increase of urinary ALA was observed, while PBG excretion tended to decline only moderately under CPZ (3.52 micrograms/day), but significantly in presence of AMT (2.16 micrograms/day). Mean values obtained from control group were 32.12 micrograms/day for ALA and 4.25 micrograms/day for PBG.

Modulation of gamma-glutamyl transpeptidase activity by dietary eicosapentaenoic acid and vitamin E in livers of rabbits on hypercholesterolemic diet.

Rabbits were fed high-cholesterol diets containing either eicosapentaenoic acid (EPA) or vitamin E at doses of 80 mg and 100 IU per day, respectively. Liver gamma-glutamyl transpeptidase (GGT) activity and liver cholesterol and phospholipid levels were determined following the administration of the diets for 45 days. The feeding of cholesterol produced the highest concentrations of cholesterol in livers accompanied with the elevated enzymatic activity. Addition of EPA to the diet dramatically reduced GGT activity to normal levels, whereas vitamin E administration caused only a slight reduction.

Gamma-glutamyl transpeptidase and acetylcholinesterase activities in brain capillaries of cholesterol-fed rabbits.

Cerebral microvascular endothelium, the constituent cell of the blood-brain barrier, is enriched in the enzyme gamma-glutamyl transpeptidase (GGT). This enzyme plays a role in the regulation of amino acid uptake and transport, and in the gamma-glutamylation of serotonin, dopamine and norepinephrine. Recent studies have demonstrated that GGT activity is modulated by cholinergic-adrenergic agonists. The levels of the acetylcholine-catabolizing enzyme acetylcholinesterase (AChE), may therefore be related to the modulation of the GGT activity. In this study, the activities of GGT and AChE in microvessel-enriched fractions were assayed after feeding of rabbits a high cholesterol diet. A 21% decrease of GGT activity and a 44% increase of AChE activity appeared at the end of dietary treatment.