No abstract

Rationale-Endocannabinoid, opioid, and dopamine systems interact to exhibit cannabinoid receptor neuromodulation of opioid peptides and D 4 dopamine receptor gene expression in CB 1 -cannabinoid-deficient mouse striatum.Objective-Using CB 1 -transgenic mice, we examine primary age-sex influences and interactions on opioid and dopamine system members' gene expression in striatum. Results-(1) Increased PPENK and PPDYN, owing to genotype [CB 1 (+/+) vs. CB 1 (−/−)], depended on sex. When genotype-independent, they depended on sex (PPENK) or age (PPDYN).(2) δ-OR was age-dependent (higher in old). (3) μ-OR, owing to genotype, was age-dependent [higher in old CB 1 (−/−) males]. When genotype-independent, it depended on sex (higher in NIH Public Access Author ManuscriptPsychopharmacology (Berl). Author manuscript; available in PMC 2013 July 11.

(1) This study investigated the functional genomics of glucocorticoid and opioid receptor stimulation in cellular adaptations using a cultured neuronal cell model. (2) Human SH-SY5Y neuroblastoma cells grown in hormone-depleted serum were treated for 2-days with the glucocorticoid receptor-II agonist dexamethasone (30 nM); the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate (DAMGO; 1 nM); or dexamethasone (30 nM) plus DAMGO (1 nM). RNA was extracted; purified, reverse transcribed, and labeled cDNA was hybridized to a 10,000-oliogonucleotide-array human gene chip. Gene expression changes that were significantly different between treatment groups and were of interest due to biological function were verified by real-time reverse transcription polymerase chain reaction (RT-PCR). Five relevant genes were identified for which the combination of dexamethasone plus DAMGO, but neither one alone, significantly up-regulated gene expression (ANOVA, P < 0.05). (3) Proteins coded by the identified genes: FRS2 (fibroblast growth factor receptor substrate-2; CTNNB1 (beta1-catenin); PRCP (prolyl-carboxypeptidase); MPHOSPH9 (M-phase phosphoprotein 9); and ZFP95 (zinc finger protein 95) serve important neuronal functions in signal transduction, synapse formation, neuronal growth and development, or transcription regulation. Neither opioid, glucocorticoid nor combined treatments significantly altered the cell growth rate determined by cell counts and protein. (4) We conclude that sustained mu-opioid receptor stimulation accompanied by glucocorticoids can synergistically regulate genes that influence neuronal function. Future studies are warranted to determine if combined influences of glucocorticoid fluctuations and opioid receptor stimulation in vivo can orchestrate exagerated neuroadaptation to reinforcing drugs under chronic mild stress conditions.

Background: Previous studies have shown that testosterone enhances baroreflex bradycardia. Therefore, conscious unrestrained rats were used to investigate the role of the androgen receptor in the testosterone-mediated modulation of baroreflex bradycardia. Androgen depletion (3 weeks), and androgen receptor blockade (20-24 h), were implemented to test the hypothesis that testosterone influences baroreflex bradycardia via its activity at the androgen receptor in male rats. Phenylephrine (1-16 µg kg -1 ) was used to assess baroreflex bradycardia.