Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Interaction of anticancer herbal drug berberine with DNA immobilized on the glassy carbon electrode.

The interaction of anticancer herbal drug berberine with double-strand DNA (dsDNA) and single-strand DNA (ssDNA) in solution, dsDNA immobilized on the glassy carbon electrode prepared by Langmuir-Blodgett technique, were investigated by electrochemical techniques (cyclic voltammetry, differential pulse voltammetry) and UV spectroscopy. The presence of DNA results in a decrease of the currents and a negative shift of the electrode potentials from the DPV curves of berberine, indicating the dominance of electrostatic interactions. The spectroscopy data confirmed that the predominant interaction between berberine and DNA is electrostatic. The binding of berberine with DNA, when analyzed in terms of the cooperative Hill model, yields the binding constant K(a)=2.2(+/-0.2)x10(4) M(-1), corresponding to the dissociation equilibrium constant K(d)=4.6(+/-0.3)x10(-5) M, which in the range of the applied concentrations of DNA (bp) and berberine, and a Hill coefficient m=1.82(+/-0.08) in Britton-Robinson buffer solution (0.05 M, pH 5.72) at T=298 K (25 degrees C). Apparently, at least two molecules of berberine have to bind as a couple to cause, e.g., the "elementary event" of current change. The results are suggestive for further fruitful applications of this anticancer herbal drug and DNA-modified electrodes.