It is well established that
5-hydroxytryptamine (5-HT; serotonin) neurons participate in the control of
sexual behavior, both in humans and in animals. The amine has been
implicated in the supraspinal as well as the spinal pharmacology of
erectile function and involves both sympathetic, parasympathetic,
and somatic outflow mechanisms. 5-HT pathways are considered to
exert a general inhibitory effect on male sexual behavior (Bitran
and Hull, 1987). However, these
pathways may be inhibitory or facilitatory depending upon the action
of the amine at different subtypes of 5-HT receptors located at
different sites in the central nervous system (de Groat and Booth,
1993). The effects also seem to be species
specific (Paredes et
al., 2000).
5-HT-positive nerve terminals are
present throughout the central nervous system, and 5-HT-containing neurons can
be found in the medullary raphe nuclei and ventral medullary
reticular formation, including the rostral nucleus
paragigantocellularis, as well as the lumbosacral spinal cord in
association with mainly somatic and autonomic outflow projections to
the pelvis (Loewy and McKellar, 1981; Steinbusch, 1981; Monroe and
Smith, 1983; Skagerberg and Bjorklund, 1985; Fischette et
al., 1987; Marson and McKenna, 1992; Tang et al., 1998;
Bancila et al., 1999) Thus, 5-HT appears to serve various functions in
male sexual function and is likely to act as a major modulator of the central
neuroregulatory control of penile erection. Many 5-HT receptor subtypes
have been identified, which can rationally be divided into G-protein-coupled
and ligand-gated ion channel-related subfamilies (Gerhardt and van Heerikhuizen,
1997; Barnes and Sharp, 1999). The receptors use different effector systems
in different cells, which may explain the conflicting reports on the
effects of 5-HT agonists and antagonists on sexual functions. For
example agonists may either enhance or depress sexual function,
which has been attributed to the involvement of multiple 5-HT
receptors. 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C
receptor subtypes have been found at different levels of the spinal cord
(Marlier et al., 1991; Thor et al., 1993; Ridet et al.,
1994).