Why SSRIs kill libido and can permanently downreagulate NAc DA release

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In short, excessive 5HT signaling can down-regulate hcrt/orx and result in the

loss of hcrt/orc neurons through the down-regulation of neuro-sex steroid

production. Low sex steroids, namely estrogen (even in men) can cause a loss of

these critical neurons.

Behavioral/Systems/Cognitive

A Role for Hypocretin (Orexin) in Male Sexual Behavior

W. Muschamp,1,4 M. Dominguez,1,5 Satoru M. Sato,2,4 Roh-Yu Shen,3 and

Elaine M. Hull1,4

.... " That such pro- jections contain hcrt/orx is supported by experiments in

which NAc DA efflux is seen to increase after intra-VTA injection of hcrt/orx

(Narita et al., 2006). Within the hypothalamus, seroto- nin [5-hydroxytryptamine

(5-HT)] can potently hyperpolarize hcrt/orx neurons in the LHA (Li et al.,

2002). Selective serotonin reuptake inhibitors or 5-HT itself, reverse dialyzed

into the LHA near the main population of hcrt/orx-expressing cells, reduces

basal and female-elicited NAc DA release and impairs copulation (Lorrain et al.,

1997, 1999). In light of data presented above show- ing activation of hcrt/orx

neurons during copulation and of VTA DA neurons by hcrt/orx, we argue that

descending hcrt/orx pro- jections to the VTA could mediate sex-related NAc DA

release. Furthermore, inhibition of these projections by intra-LHA 5-HT may

explain the inhibitory effect of 5-HT on NAc DA release and sexual behavior. "