Effects of endophyte-infected tall fescue, environmental temperature and prazosin injection on the rat.

Effects of an alpha 1 antagonist, prazosin, injection on the rat (Rattus rattus) exposed to warm vs normal environments and fed endophyte-infected (E+) or -free (E-) tall fescue seed were studied. Rats were injected IP daily with placebo or prazosin (1 mg/kg BW). Daily skin and rectal temperatures and food intake measurements were recorded. Selected brain tissues were dissected to determine treatment effects on monoamine receptor density. Rats fed E+ and injected with placebo had reduced (P < 0.01) food intake compared with all other treatments. By day 5 of injection, an endophyte x temperature interaction for increased (P < 0.03) skin and rectal temperatures was measured when rats were fed E+ and housed at 32 degrees C. Also by day 5, injection of rats consuming E+ with prazosin reduced (P < 0.01) skin and rectal temperatures 0.4 degree C compared with those consuming E+ and injected with placebo. Monoamine receptor (alpha 1, alpha 2, and D2) densities were similar (P > 0.10) among treatments. Prazosin injection reduced E+ induced body temperature increases chronically and increased food intake acutely to E- levels. Monoamine receptor densities were unchanged; therefore, E+ effects via monoamine receptors may be due to acute modulation of receptor-associated activity.

Ergovaline binding and activation of D2 dopamine receptors in GH4ZR7 cells.

Ergovaline inhibition of radioligand binding to the D2 dopamine receptor and ergot alkaloid inhibition of vasoactive intestinal peptide (VIP)-stimulated cyclic AMP production in GH4ZR7 cells, stably transfected with a rat D2 dopamine receptor, were evaluated. Ergovaline inhibition of the binding of the D2-specific radioligand, [3H]YM-09151-2, exhibited a KI (inhibition constant) of 6.9 +/- 2.6 nM, whereas dopamine was much less potent (370 +/- 160 nM). Ergot alkaloids were also effective in inhibiting VIP-stimulated cyclic AMP production, with EC50 values for ergovaline, ergonovine, alpha-ergocryptine, ergotamine, and dopamine of 8 +/- 2, 47 +/- 2, 28 +/- 2, 2 +/- 1, and 8 +/- 1 nM, respectively. Inhibition of cyclic AMP production by ergovaline was blocked by the dopamine receptor antagonist, (-)-sulpiride (IC50, 300 +/- 150 nM). Our results indicate that ergot compounds, especially ergovaline, bind to D2 dopamine receptors and elicit second messenger responses similar to that of dopamine. These findings suggest that some of the deleterious effects of consumption of endophyte-infected tall fescue, which contains several ergot alkaloids including ergovaline, may be due to D2 dopamine receptor activation.

D2 dopamine receptor response to endophyte-infected tall fescue and an antagonist in the rat.

Effects on rat brain D2 dopamine receptors by endophyte-infected tall fescue seed consumption and antagonist injection were characterized. Forty-eight male Wistar rats (225 g) in three separate trials were exposed to either 22 or 32 degrees C. Diets, to maintain similar concentrations of ergovaline, contained 10% (Trial 1) or 15% (Trials 2 and 3) endophyte-infected (E+; 325 average ppb of ergovaline) or uninfected (E-; 0 ppb of ergovaline) tall fescue seed. Rats were injected i.p. daily with either placebo (PL) or an experimental D2 dopamine antagonist (DA, .0375 mg/kg BW). No effects (P > .10) on diet DM intake by E+ ingestion or DA injection were detected at 22 degrees C. However, ingestion of E+ reduced (P < .01) and injection of DA improved (P < .05) DM intake of rats housed in 32 degrees C (11.1 vs 15.4 g of DM/d for E+ vs E-, respectively). Whole brain D2 dopamine receptor density (Bmax) and mRNA were reduced (P < .05) by E+ and increased (P < .05) by DA in Trial 1. No treatment effects (P > .10) on cerebral cortex alpha 1- and alpha 2-adrenergic or striatal D2 dopamine receptor Bmax were measured in Trials 2 and 3. In summary, dietary E+ reduced whole brain D2 dopamine mRNA and Bmax, whereas injection of DA increased D2 dopamine mRNA. Thus, long-term regulation of monoamine receptors seems to be affected by E+ ingestion or DA injection.

Embryonic mortality in Sprague-Dawley rats induced by snakeweed (Gutierrezia microcephala).

Three experiments were conducted to determine the effects of ingested snakeweed foliage (SW) on gestating rat embryos. Mature female Sprague-Dawley rats were paired with male rats and after breeding were randomly allotted to diets containing up to 15% SW. Feeding SW caused a decrease (P < .01) in the percentage of live embryos and markedly increased (P < .01) the percentage of dead or resorbed embryos. Snakeweed decreased (P < .01) feed intake in a dose-dependent manner and caused BW loss (P < .01) compared with control animals. However, decreased feed intake had no effect on gestating embryos. Rats fed the control diet, with intakes restricted to equal the average intake of rats fed SW, and those with ad libitum access to the control diet had similar percentages of live and dead embryos (P > .10). Serum clinical profiles reflected undernutrition (decreased triglycerides and cholesterol; P < .01) and mild toxicosis (elevated blood urea nitrogen, creatinine, and bilirubin; P < .01). Because fluid accumulation was noted in the uterus of several rats fed SW, a uterine weight bioassay was conducted. Snakeweed, fed as 10% of the total diet, decreased (P < .01) uterine weight of immature Sprague-Dawley rats. Ingestion of SW during early gestation caused embryonic mortality that could not be attributed to undernutrition or estrogenicity.