Modeling Human Sexual Motivation in Rodents: Some Caveats

Abstract

Sexual behavior is activated by motivation. An overwhelming majority of experimental studies of the intricacies of sexual motivation has been performed in rodents, most of them in rats. Sometimes it is desirable to generalize results obtained in this species to other species, particularly the human. It is hoped that studies of the neurobiology of rodent sexual behavior may shed light on the central nervous mechanisms operating in the human, and the search for efficient pharmacological treatments of human sexual dysfunctions relies partly on studies performed in rodents. Then the issue of generalizability of the rodent data to the human becomes crucial. We emphasize the importance of distinguishing between copulatory acts, behavior involving the genitals, and the preceding event, the establishment of physical contact with a potential mate. Comparisons between the structure of copulatory behavior in rats and humans show abysmal differences, but there may be some similarity in the underlying mechanisms. The endocrine control of sex behavior is shortly mentioned, and we also compare the effects of the few drugs known to affect both rodent and human copulatory behavior. The stimuli activating sexual motivation, often called desire in the human literature, are examined, and the sexual approach behaviors in rats and humans are compared. There is a striking similarity between these species in how these behaviors respond to drugs. It is then shown that the intensity of sexual approach is unrelated to the intensity of copulatory behavior. Even though the approach is a requisite for copulation, an activity that requires at least two individuals in close physical contact, these two aspects of sexuality do not covary. This is similar to the role of the testosterone in men and male rats: although the hormone is needed for sex behavior, there is no correlation between serum testosterone concentration and the intensity of copulation. It is also pointed out that human sexual behavior is mostly determined by social conventions, whereas this is not the case in rats and other rodents. It is concluded that some observations in rats can be generalized to the human, but extreme caution must be exercised.

Keywords: ejaculation; lordosis; orgasm; paracopulatory behavior; sexual behavior; sexual motivation.

Figure 1

A model for sexual incentive motivation. The text in italics represents the example of the male rat. (a) A reciprocal excitatory relationship functioning in such a way that the central motive state enhances the sensory system’s sensibility to stimuli with sexual significance. When such stimuli are perceived, the sensory system excites the central motive state which in turn further sensibilizes the sensory system, i.e., the relationship is one of reciprocal positive feedback. (b) At a certain threshold level of activity, the central motive state engages a series of viscerosomatic activities preparing the subject for sexual interaction. (c) The appropriate environmental stimuli activate motor patterns that bring the subject in contact with the source of stimulation. During approach, additional incentive stimuli may be encountered. These will be centrally represented and enhance the central motive state through (a). (d,e) Provided that approach behaviors have been successful and that appropriate viscerosomatic reactions are being accomplished, the subject’s behavior may change from unconditioned or conditioned instrumental responses to the execution of sexual reflexes. These are activated by tactile stimulation of the perineal or lower abdominal region. If the subject is sexually inexperienced such stimulation is obtained accidentally. If the subject already has acquired sexual experience, then conditioned instrumental responses may facilitate the attainment of tactile stimulation necessary for activation of sexual reflexes. At the point of transition from approach to execution of copulatory reflexes, the behavioral sequence is aborted in the absence of tactile stimulation. In case that sexual reflexes indeed are activated, sex behavior will normally continue until ejaculation. (f) The positive affect induced by ejaculation will feed back to the central motive state where a short-lasting inhibitory system is activated. (g) At the same time, the positive affect and associated processes of reinforcement will strengthen the learning of associations between itself and environmental cues. These cues will acquire incentive properties in relation to the intensity of the positive affect that is experienced. For further details, see Ågmo (1999, 2011) and Paredes and Ågmo (2004). Reprinted from Ågmo (1999). Copyright (1999), with permission from Elsevier.

Figure 2

van de Velde’s (1926) illustration of human coital interactions. (A) The changes in sexual excitation during an ideal copulatory encounter. With ideal it is understood that the man and the woman reache orgasm at the same time. Excitation is defined as the summation of sexual desire and pleasure, bodily and psychic. (B) Similar to panel (A), but here the sexual interaction occurs with an inexperienced woman without adequate coital stimulation. (C) Similar to panel (A), but now the woman is sexually experienced. The prelude was omitted, but the woman’s low initial excitation was compensated for by her experience. From van de Velde (1926).

Figure 3

Sexual behavior in a cage in which the female can escape from the male copulation partner. The female is present already at the beginning of the timeline. The horizontal, double-ended black arrows represent the time the female has escaped from the male into her own half. The illustration ends after the first intromission following the first ejaculation. Copulation may have continued for several ejaculations, however.

Figure 4

Sexual behavior displayed by male rats in a seminatural environment during females’ natural estrus. There were three males in the environment. Time 0 represents the beginning of estrus, i.e., when the female or females presented their first lordosis. A copulatory bout (CB) is a period of continuous (adjacent copulatory events are separated by less than 60 min) male sexual activity. (A) One single female is in estrus. All males copulate with the female during overlapping periods. (B) Three females are in estrus simultaneously. Each male copulates with the three females, and each female copulates with all the males in overlapping periods. Rat copulatory behavior seems to be entirely promiscuous, perhaps similar to what is observed in sex clubs frequented by humans (see “Multiple Orgasms and Ejaculations” section). For further details, see Chu and Ågmo (2015b). Reprinted with permission from the American Psychological Association.

Figure 5

Parameters of copulatory behavior in male rats treated with fluoxetine, 10 mg/kg per day orally, or saline for 15 days. The test on Day 0 was performed 1 h after the first fluoxetine administration. (A) Intromission latency. Analysis of variance (ANOVA) for repeated measures on the factor Day of treatment and independent measures on the factor Treatment failed to reveal any statistically significant effect of Treatment, of Day of treatment and of the interaction Day × treatment (all ps > 0.07). (B) Number of intromissions. Also here, ANOVA failed to detect any significant effect (all ps > 0.51). (C) Interintromission interval. No effect (all ps > 0.39). (D) Ejaculation latency. No effect (all ps > 0.13). Data are mean ± standard error of the mean (SEM). Data are from an unpublished experiment, performed by one of the present authors (AÅ) together with Juoni Sirviö, Gro Sandberg and Live Sørensen.

Figure 6

Paracopulatory behaviors displayed by female rats tested in a divided cage until the male had achieved five ejaculations. We determined the number of those behaviors displayed in the male’s half as well as the number displayed in the female’s half during the 1st and 5th ejaculatory series. (A) The rate expressed as number per minute of paracopulatory behavior. Two-factor ANOVA with repeated measures on one factor (Series) revealed a main effect of Series (F_(1,6) = 20.269, p = 0.004) but not of Side (female, male; F_(1,6) = 0.778, p = 0.412). The interaction Series × Side was also non-significant (F_(1,6) = 1.326, p = 0.293). (B) Number of behaviors. ANOVAs found no effect (all ps > 0.24). (C) Male copulatory behavior. The number of intromissions performed during the 1st and 5th series was similar (t₍₆₎ = 0.786, p = 0.462, paired t-test). The rate of intromission, calculated as number per minute, was lower in the 5th series than in the 1st (t₍₆₎ = 2.691, p = 0.018). Data (mean ± SEM) are from an experiment performed by Ellinor Ellingsen and Ana Lene Turi. *Different from 1st series (p < 0.05).

Figure 7

A photograph of the sexual incentive motivation test arena. The incentive animal cages (marked with an A on the photograph) are located on the outside of the oval arena (100 × 50 cm). They are detachable from the outside of the wall so that the position of the incentive animals can be changed randomly. The side facing the arena is made of a wire mesh that allows the experimental subject to see, smell and hear the incentives. A virtual zone of 21 × 29 cm (marked with a B on the photograph) is defined outside each incentive animal cage. A computerized videotrack system determines the experimental subject’s position, the time spent in the incentive zones, the number of visits to them, the distance moved during the test, the mean speed of movement while moving, and the immobility time. Reproduced from Spiteri and Ågmo (2006). Copyright 2006, republished with permission from Elsevier.

Figure 8

Sexual approach behavior in male rats in response to different kinds of stimuli (black bars). As control for social approach, an intact male was used (gray bars). The experimental subject could choose between spending its time close to the male stimulus or close to the alternative stimulus. The ordinate shows time spent in proximity to the different stimuli. The stimuli are indicated on the abscissa. 1. An intact male and an empty, clean cage, N = 11. The time spent close to the male was far superior to the time spent close to the empty cage. This illustrates nicely the male’s social attraction. 2. An intact male and a sexually receptive female, N = 10. The difference between the time spent with the female and the time spent with the male is the intensity of sexual attraction [(sexual + social approach) – social approach] = sexual approach. 3. Intact male and playback of female ultrasonic vocalizations, N = 10. As can be seen, the vocalizations were not more attractive than a silent, empty cage. 4. Intact male and the odor of a sexually receptive female, N = 11. The female had spent 6 h in the cage before being removed just before the test. She left behind urine, feces and other body odors that may stick to the floor and walls of the small cage. The odor was not more attractive than the male. Thus, odor by itself has no sexual attractant properties according to our definition (see Stimulus 2). 5. As always, an intact male. The other stimulus was here an anesthetized female and the experimental subject was anosmic. Thus, the only stimulus modality available to the male was vision, N = 9. Neither of the stimuli was more attractive than an empty cage. Thus, olfaction is necessary for social as well as for sexual approach. Visual stimuli have no impact. 6. Intact male and a devocalized female were the available stimuli, and the experimental subject was anosmic. The test was performed in complete darkness. Thus, neither visual nor olfactory stimuli were available, and no stimuli from the female’s vocal cords, N = 10. None of the stimuli was attractive to the experimental male. 7. Intact male and the odor of a female + playback of female ultrasonic vocalizations were the alternatives, N = 10. Both were equally attractive, showing that odor + vocalizations have no sexual attractant properties. 8. Intact male and anesthetized female + playback of vocalizations. The experimental subject was anosmic, N = 9. There was no difference between these latter stimuli and an empty cage, showing that the sight and vocalizations from a female does not attract a male at all. 9. Intact male and sexually receptive female. The experimental subject was anosmic, and the test was performed in complete darkness. The only stimulus available to the male was auditory, N = 10. They did not produce sexual attraction. 10. Intact male and anesthetized female, providing olfactory and visual stimulation but no sounds, N = 11. She was as attractive as an active female. 11. Intact male and devocalized female, test performed in complete darkness, N = 9. This female was as attractive as an intact female. 12. Intact male and devocalized female. The subject was anosmic, N = 10. No social or sexual attractivity was observed. *Different from the social incentive (male rat), p < 0.05. ^aDifferent from the empty cage (stimulus 1), p < 0.05. The conclusion from this experiment was that olfactory stimuli need to be combined with some other stimulus in order to activate sexual attraction. The other stimulus cannot be produced by the female’s vocal cords. Further details can be found in Ågmo and Snoeren (2017).

Figure 9

The effects of fluoxetine, 10 mg/kg and day given orally, on sexual approach behaviors in male rats. The procedure described in “Sexual Approach in Rodents” section was used. Test duration was 10 min. The acute test was performed 60 min after drug administration. (A) Preference score. Mixed two-factor ANOVA with Treatment and Day as factors revealed a significant Treatment effect (F_(1,34) = 7.528, p = 0.010), but there was no effect of Day (F_(3,102) = 0.192, p = 0.902) and no interaction Treatment × Day (F_(3,102) = 1.239, p = 0.300). (B) Time spent in the vicinity of the social incentive (another male) and in the vicinity of the sexual incentive (receptive female rat). Three-factor ANOVA with the factors Incentive, Treatment and Day found an effect of Incentive (F_(1,34) = 86.072, p < 0.001) and of Treatment (F_(1,34) = 7.134, p = 0.012) but not of Day (F_(3,102) = 1.789, p = 0.154). The time spent in the vicinity of the female was superior to that spent in the vicinity of the social incentive at all tests according to the Tukey HSD test. There was also an interaction between Incentive and Treatment (F_(1,34) = 7.993, p = 0.008). Fluoxetine did not alter the time spent in the vicinity of the male incentive whereas the time spent in the vicinity of the sexual incentive was reduced. There were no other interactions (ps > 0.300). Thus, fluoxetine did not modify social approach but reduced sexual approach. Since there was no interaction Treatment × Day, this effect was present already at the acute test. (C) The distance moved during the test, a measure of ambulatory activity, was not altered by treatment and did not vary between days (ps > 0.102). Thus, the inhibition of sexual approach cannot be explained as a secondary effect of reduced activity. Data are mean ± SEM. *Different from saline, p < 0.05. From an unpublished experiment performed by AÅ, Juoni Sirviö, Gro Sandberg and Live Sørensen.