Although definitive research elucidating the complex neurobiological substrates of sexual behavior in humans is lacking, laboratory research of mammalian sexual behavior and monoamine neurotransmitters offers some potentially valuable data that might help to identify a biological substrate for sexual behaviors, including PAs and PRDs, in humans. If such a substrate could be identified, it might represent the focus for treatments of these disorders. Laboratory-derived mammalian data suggest that decreased central (i.e., brain) serotonin (5-hydroxytryptamine [5-HT]) may disinhibit or promote sexual behavior (Ferguson et al. 1970; Sheard 1969; Tagliamonte et al. 1969) and, conversely, that enhancing central serotonin activity may inhibit sexual behavior in some mammalian species (Everitt and Bancroft 1991; Tucker and File 1983). In humans as well, enhancing central serotonin neurotransmission inhibits sexual desire and associated sexual behaviors. For example, the selective serotonin reuptake inhibitors (SSRIs) clomipramine, fluoxetine, sertraline, fluvoxamine, paroxetine, and citalopram increase postsynaptic serotonergic effects, and all have been reported to produce a high frequency of sexual dysfunction “side effects,” including the cluster of loss of sexual desire and impaired sexual response (ejaculatory delay, erectile dysfunction, and anorgasmia) (Labbate et al. 1998).

In mammalian species, decreased central dopaminergic neurotransmission will reduce motivated as well as appetitive drive behavior, including male sexual behavior (Baum and Starr 1980; Everitt 1983; Malmnas 1973; Mas 1995; Segraves 1989). Conversely, pharmacological enhancement of dopaminergic neurotransmission may augment male sexual behaviors (Everitt 1990; Everitt and Bancroft 1991; Mas 1995; Paglietti et al. 1978). In humans, dopamine type 2 receptor blockade with traditional antipsychotics diminishes sexual appetite and has been used to reduce paraphilic arousal (Tennent et al. 1974; Field 1973). Conversely, increased sexual desire, as measured by self-report of fantasies, erections, and activities, has been reported in men treated with dopamine agonists such as l-dopa (Bowers et al. 1971; O’Brien et al. 1971) and amphetamine (Angrist and Gershon 1976; Bell and Trethowan 1961). Finally, serotonergic and dopaminergic functional systems interact in the medial preoptic area of the hypothalamus and the nucleus accumbens, areas associated with the modulation of sexual appetitive behavior (Alcantara 1999).

It has also been reported that the “sex” hormones estradiol, testosterone, and progesterone can induce alterations in the binding of monoamine neurotransmitters in the limbic system, suggesting that one of the cellular mechanisms of hormone action may be at the level of monoamine receptors - the modulation of serotonin, dopamine, and norepinephrine (Baum and Starr 1980). In male rats, for example, testosterone may affect the changes in central serotonin concentrations that accompany sexual maturity (Kendall and Tonge 1976), thereby inducing alterations in the binding of norepinephrine, dopamine, and serotonin in the hypothalamus (Baum and Starr 1980). It is possible, then, that in humans, sex hormones and monoamine neurotransmitters interact in a dynamic fashion that determines the form and intensity of drive behaviors, including sexual behavior (Baum and Starr 1980; Sicuteri 1974). The precise delineation of the interrelationship of these hormone-monoamine systems in humans may hold exciting clues to the biological substrates of sexual behaviors, normal as well as possibly pathological.

The neurobiological substrates of impulsivity, compulsivity, anxiety, and depression - comorbid psychological states, as well as Axis I diagnoses associated with PAs and PRDs - are better elucidated in humans than are the substrates of sexual behavior. Animal and human studies have consistently pointed to an association between reduced central serotonin neurotransmission and the release of suppressed behaviors (Soubrie 1986), including impulsive behaviors and aggression (G. L. Brown and Linnoila 1990; Coccaro 1989; Insel et al. 1990; Kavoussi and Coccaro 1993; Linnoila et al. 1983; Stein et al. 1993). Central serotonergic disturbance may accompany some depressive disorders (Meltzer 1990; Risch and Nemeroff 1992), anxiety disorders (Kahn et al. 1987; van Praag et al. 1987), and consummatory behaviors (Amit et al. 1991), including alcoholism (Amit et al. 1991).

Dopamine appears to be associated with the mobilization, facilitation, and sustenance of goal- or incentive-related behavior (Blackburn et al. 1992; Crow 1973; van Praag et al. 1990), and impairment in dopamine neurotransmission may mediate impulsivity and inattentiveness characteristic of ADHD (Levy 1991). In addition, dopaminergic agonists such as l-dopa or psychostimulants can enhance or disinhibit sexual appetitive behavior, and dopaminergic antagonists such as traditional antipsychotics can diminish sexual appetitive behavior. These data, taken together, provide the scaffolding for a monoamine hypothesis for the pathophysiology of PAs (Kafka 1997b) and PRDs.