5-HT also promotes an efflux of DA through reversal of the direction of DA transport. By analogy with the mechanism of action described for amphetamine, the consequences of 5-HT entering DA terminals might explain both the excitatory and inhibitory effects of 5-HT on presynaptic DA terminal activity, but the physiological relevance of this mechanism is far from clear. The recent data suggest that the endogenous 5-HT system affects striatal DA release in GSK923295 mouse a state-dependent manner associated with the conditional involvement of various 5-HT receptors such as 5-HT(2A), 5-HT(2C), 5-HT(3), and 5-HT(4) receptors.

Methodological and pharmacological issues have prevented

a comprehensive overview of the influence of 5-HT on striatal DA activity. The distribution of striatal 5-HT receptors

and their restricted influence on DA neuron activity suggest that the endogenous 5-HT system exerts multiple and subtle influences on DA-mediated behaviors.”
“We explored the attenuating effects of NP-9 on beta-amyloid (A beta) aggregation and amyloid-induced toxicity. NP-9 is a recently reported monoamine oxidase B (MAO-B), and acetylcholinesterase (AChE) inhibitor. In the present study, we found that NP-9 inhibited AChE activity in a dose-dependent manner with a maximal inhibition dose of 8 mg/kg, i.p. It inhibited A beta aggregation, observed through thioflavin-T assay (IC50 = 60 mu M) and scanning electron GSKJ4 microscopy (S.E.M.) (no fibril formation). NP-9 has shown marked protection against scopolamine and Levetiracetam A beta(1-42)-induced memory impairments. It also minimized neuronal loss and amyloid plaque deposition in the brains

of A beta(1-42)-induced mice model. Therefore, NP-9 could be a promising lead molecule for AD, with effects against MAO-B, AChE, A beta aggregation, and A beta(1-42) induced toxicity. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Dysfunction of serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states.

Here, we highlight the methods that have been used to investigate the heterogeneity of serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of serotonergic neurons in the midbrain and pontine raphe complex.

The emerging understanding of the topographically organized synaptic regulation of brainstem serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of serotonergic systems.