**6. References**

Agmo, A., Turi, A. L., Ellingsen, E., and Kaspersen, H.2004Preclinical models of sexual desire: conceptual and behavioral analysesPharmacol.Biochem.Behav.783379404

Ahlenius, S., Larsson, K., and Fernandez-Guasti, A.1989Evidence for the involvement of central 5-HT1A receptors in the mediation of lordosis behavior in the female ratPsychopharmacology (Berl).984440444

the females were treated. 8-OH-DPAT induced increased aggression between pairmates after treatment of females alone (Aubert et al. 2009). The result is that flibanserin is clearly not a typical 5-HT1A receptor agonist, but has unique properties that contribute to its

A key to the difference in flibanserin pharmacology is it's ability to act only at post-synaptic 5-HT-1A receptors. A study by Marazziti et al. demonstrated that in human brain, flibanserin has low nanmolar potency at 5-HT1A receptors in the prefrontal cortex, but none at 10M in the dorsal raphe nucleus (Marazziti et al. 2002). The 5-HT1A receptors in the dorsal raphe nucleus are responsible for regulating serotonin release throughout the brain and typical 5-HT1A agonists will inhibit this release. Post-synaptic receptors are located outside of the dorsal raphe nucleus and have many different functions, including regulating release of all monoamines. To determine how flibanserin administration affects monoamine release two microdialysis studies were undertaken. The first investigated acute dosing while measuring serotonin, dopamine, and norepinephrine in three regions of the brain: the prefrontal cortex, the dorsal raphe, and the hippocampus (Invernizzi et al. 2003). The surprising result was that flibanserin administration decreased serotonin in the prefrontal cortex and dorsal raphe, but not the hippocampus. Recent evidence suggests that hippocampal serotonin is regulated primarily by presynaptic 5-HT1A receptors within the dorsal raphe, so the interpretation for this study is that by acting only at post-synaptic receptors flibanserin can affect serotonin release in selected brain areas. The following microdialysis study indicated that dopamine and norepinephrine are also affected in regionally selective patterns upon chronic dosing (Allers et al. 2010a). Potentially the most significant finding was that within the prefrontal cortex, an area important for general arousal and motivation, basal levels of dopamine and norepinephrine were increased selectively in the prefrontal cortex out of the regions studied (prefrontal cortex, nucleus

HSDD patients have been shown to have altered cortical reactivity and demonstrate differences in attending to sexual cues (McCall et al. 2006; Vardi et al. 2009). Flibanserin, by increasing two neurotransmitters known to be involved in sexual desire, selectively in regions responsible for attention and awareness, may act to restore these functions (Stahl et

In conclusion, the development of centrally acting clinically efficacious drugs (albeit none yet with FDA approval) to treat sexual dysfunction, and the development of new models for assessing drug effects preclinically has given the sexual sexual function research field a much needed boost. New models of dysfunction can now be validated as they are

Agmo, A., Turi, A. L., Ellingsen, E., and Kaspersen, H.2004Preclinical models of sexual desire: conceptual and behavioral analysesPharmacol.Biochem.Behav.783379404 Ahlenius, S., Larsson, K., and Fernandez-Guasti, A.1989Evidence for the involvement of

central 5-HT1A receptors in the mediation of lordosis behavior in the female

developed and translation to human dysfunction can be better established.

ratPsychopharmacology (Berl).984440444

mechanism of action.

al. 2011).

**5. Conclusions** 

**6. References** 

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**6** 

*Russia* 

**Development of Male Sexual Function After** 

**Prenatal Modulation of Cholinergic System** 

Alekber Bairamov1, Alina Babenko1, Galina Yukina2, Elena Grineva1,

*Nord-West Division of the Russian Academy of Medical Science, St. Petersburg,* 

Embryonal period of ontogenesis plays an important role in the brain development which is defined, first of all, by genetical factors. Normal flow of the process can be disturbed also under the influence of many environmental factors which affect, both a differentiation of neurones, and on a neurotransmitter choice in them used for communications with the proximate cells (Le Douarin, 1981; Pendleton, 1998). The majority of the factors attacking developing brain during this period, break a normal ontogenesis of neurotransmitter systems: NA, 5-HT, DA and ACh that shows high sensitivity of a brain in critical periods of

A variety of neurochemical changes in the embryonic brain, induced by exposure to neurotropic compounds during the prenatal period, result in the development of functional impairments and behavioral disorders in the adult offspring. The mechanisms of action of many chemical factors on the developing fetal brain during early ontogenesis are in most cases mediated by alterations in the formation and functioning of brain neurotransmitter systems, including the cholinergic system, whose CNS function is associated with memory, learning, and behavioral processes (Yamada et al., 1986; Buzsaki, 1989; Everitt & Robbins, 1998; Levin & Slotkin, 1988; Zoli et al., 1999). During the period of neuron development, actions on cholinergic mechanisms lead to delays in cell differentiation which correlate with cognitive and behavioral deficits in fertile offspring (Yamada et al., 1986; Levin & Simon,

Prenatal exposure to neurotoxins (nicotine, organochlorine compounds, barbiturates), which have cholinotropic properties, produces long-lasting changes in neurotransmitter functions in early ontogenesis with the subsequent development of neurobehavioral anomalies and affective disorders in pubescent individuals (Seidler et al., 1992; Barinaga, 1996; Slotkin, 2004). Thus, embryonic exposure to nicotine leads to alterations to cell proliferation and differentiation, resulting in long-term changes to synaptic function (Peters, 1986; Lichtensteiger, 1988). Binding to N-cholinergic receptors in catecholamine-containing neurons in the fetal brain, nicotine disrupts the expression of these transmitters

the development (Williams, 1992; Oliff, 1999; Qiao, 2004).

**1. Introduction** 

1998; Beer et al., 2005).

Boris Komikov2, Petr Shabanov3 and Nikolay Sapronov3 *1Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, 2Saint Petersburg State Medical Academy named after I. I. Mechnikov,* 

*3Institute Experimental Medicine,* 

