Peripheral and Central Administration of a Selective Neuropeptide Y Y1 Receptor Antagonist Suppresses Ethanol Intake by C57BL/6J Mice

BACKGROUND: Neuropeptide Y (NPY) is a 36–amino acid neuromodulator that is expressed throughout the central nervous system. Recent genetic and pharmacological evidence suggests that the NPY Y(1) receptor modulates ethanol intake. To further characterize the role of the Y(1) receptor, we examined voluntary ethanol consumption by mice after administration of [(−)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-tiazol-2-yl)ethyl]-4-morpholinopyridine] (compound A), a novel and selective Y(1) receptor antagonist (Y1RA) that acts centrally on brain receptors when administered peripherally. METHODS: C57BL/6J mice were habituated to drinking a 10% (v/v) ethanol solution by using a two-bottle-choice procedure and were then given an intraperitoneal (ip) injection (5 ml/kg) of the Y1RA (0, 25, 50, or 75 mg/kg). In a second study, mice were given intracerebroventricular infusion of the Y1RA (0, 30, or 100 μg). Finally, we determined whether the Y1RA alters open-field locomotor activity, ethanol-induced sedation (3.8 g/kg, ip), or blood ethanol levels. RESULTS: Relative to control treatment, ip injection (50 and 75 mg/kg) and intracerebroventricular infusion (100 μg) of the Y1RA significantly reduced ethanol consumption and food intake without altering water drinking. However, the Y1RA did not alter open-field locomotor activity, ethanol-induced sedation, or blood ethanol levels. CONCLUSIONS: These data indicate that acute blockade of the NPY Y(1) receptor with a systemically bioavailable NPY Y1RA reduces voluntary ethanol consumption by C57BL/6J mice. These results are consistent with observations that hypothalamic infusion of NPY increases ethanol drinking by rats

Analysis of genetic control of â-carotene and L-ascorbic acid accumulation from a wild cherry orange-brownish tomato accession

[EN] An additive-dominance, additive 9 additive (ADAA) and genotype 9 environment interaction mix model was used to study the genetic control of beta-carotene and L-ascorbic acid in six basic generations (P-1, P-2, F-1, F-2, BC1P1 and BC1P2) of tomato derived from the cross CDP8779 accession (Solanum lycopersicum L.) x CDP4777 accession (S. lycopersicum var. cerasiforme). The study was performed in two environments: (1) open field; (2) protected environment, consisting of hydroponic cultivation in a glasshouse. The results indicate that beta-carotene accumulation was mainly additive (32.2% of the genetic component), with a small dominant component (4.2%) and an important additive x environment interaction contribution (63.6%). In target environments with moderate to high temperatures and no limiting radiation, this the expression additive x environment interaction could substantially enhance the beta-carotene content. This trait showed also a high narrow-sense heritability (h(2) = 0.62). Ascorbic acid accumulation was also mainly additive (61.7% of the genetic component), with a minor additive epistatic component (21.5%). This epistatic effect caused a negative heterosis that reduced the positive main additive effect. Nevertheless, in the described target environments, the additive 9 environment interaction contribution (16.8%) may enhance the ascorbic acid content and compensate for the negative heterosis effect. The total narrow-sense heritability of this trait can be considered useful (h(2) = 0.52). In conclusion, the CDP4777 accession is a very interesting donor parent for the joint improvement of beta-carotene (without diminishing lycopene content) and ascorbic acid content in commercial nutraceutical tomato breeding programmes; the F-1 hybrids derived from this accession showed nearly 450% of the commonly reported average beta-carotene content and close to 130% of the ascorbic acid content of the female parent.This research was financed by the Spanish Ministry of Science and Innovation (MICINN) (project AGL2005-08083-C03-01). The authors thank Dr. Luis Mejia and the Universidad de San Carlos of Guatemala for providing the CPD4777 accession, among others. The authors thank Professor Jun Zhu, director of the Bioinformatics Institute, Zhejiang University, China, for his comments and for kindly providing the software used in the data analyses.Adalid Martinez, AM.; Rosello Ripolles, S.; Valcárcel Germes, M.; Nuez Viñals, F. (2011). Analysis of genetic control of â-carotene and L-ascorbic acid accumulation from a wild cherry orange-brownish tomato accession. Euphytica. 184(2):251-263. doi:10.1007/s10681-011-0584-xS251263184