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This research is still in its infancy Apart from behavioral studies, there is a need for standardization and more research is de nitely mandatory in this area There is no model available, for example, to investigate delayed or absent ejaculation or painful ejaculation, and the experimental equivalent of the male orgasm is lacking
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Sexual motivation and desire
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Desire has always been dif cult to de ne objectively In the DSM-IV-TR, the diagnosis of hypoactive sexual desire disorder is given when desire for and fantasy about sexual activity are chronically or recurrently de cient or absent By converse logic, then sexual desire is the presence of desire for, and fantasy about, sexual activity This de nition appears coherent but is circular How does desire manifest itself Like people, animals manifest sexual excitement behaviorally They increase their motor output in anticipation of copulation and work for the opportunity to copulate or to obtain primary or secondary (conditioned) sexual rewards associated with copulation Animals will also choose between two or more sexual incentives based on the strength of the incentive cues and the animal s own internal drive state What characterizes these behaviors is that they occur before copulation: Courtship, operant responses, conditioned locomotion in anticipation of sex, time spent near a particular sexual incentive, or choices made between two or more incentives, can all be considered analogies of anticipatory sexual desire The strength of the behavior can be observed as increases or decreases, or can be tested by increasing the crite-
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Orgasm and the consequences of ejaculation
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Although it is not known whether male rats experi-
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Preclinical Research and Animal Models in Sexual Medicine rion level of responding that animals must attain before they are given access to rewards Simply put, animals with more desire will display more robust behavior than animals with less desire Desire can also be inferred from certain appetitive responses that occur during copulation, such as solicitation in females or chasing behavior in males A growing body of evidence indicates that these aspects of sexual behavior are altered in a relatively selective fashion by certain drugs that are known to alter desire in humans (eg by drugs that affect dopamine or melanocortin receptors)
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Models of male sexual dysfunctions Erectile dysfunction
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Male rats that do not perform sexually are typically taken out of behavioral studies, so there is very little known about their actual erectile responsiveness This proportion is generally low, especially if the males are pre-exposed to the test chambers prior to their initial sexual experiences Some of these males do not display any interest in the female, and do not initiate any kind of sexual activity However, other males display sexual interest and mount repeatedly, but do not achieve vaginal intromission The lack of intromission may stem from an inability to achieve erection Indeed, erectile responses in isolation and intromissions during copulation are both very sensitive to disruption by several classes of drug, including psychomotor stimulants, dopamine and noradrenergic antagonists, and opioid agonists Acute or chronic treatment with selective serotonin reuptake inhibitors (SSRIs) does not appear to alter erectile responses or the number of intromissions prior to ejaculation This pro le of pharmacologic sensitivity is strikingly similar to clinical observations and anecdotes in men, thus male rats may be a useful model of drug-induced, if not also stress or vascular disease related erectile dysfunction
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In 1956, Knut Larsson published a series of studies that described many ways in which sexual re exes and behaviors could be conditioned by experience In one of these paradigms, called the enforced interval effect , male rats were given repeated access to females that were removed physically from the
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testing chamber by the experimenter after every intromission In this way, Larsson was able to vary the time between intromissions and found that male intromission intervals that lasted longer than normal resulted in males that learned to ejaculate with far fewer intromissions One of the interpretations of this data was that the imposition of longer intromission intervals made males more sympathetically aroused, and led to either a faster ejaculation or one that required less tactile penile stimulation This model of hyperstimulation of sympathetic out ow by either highly stimulating, unpredictable, or stressful sex, formed part of the basis of Masters and Johnson s model of premature ejaculation a decade later Despite this, the model has not been developed further, nor has it been used widely to examine drug effects More recently it was reported that natural differences are found in the ejaculation latencies of male rats, which may indicate a more biological explanation of premature ejaculation that shares some of the characteristics of human premature ejaculation In pooled populations of male albino Wistar rats during a 30 min standardized mating test, three categories of males were identi ed: (1) males that displayed a low number of ejaculations (0 to1) and were considered as sexually sluggish or hypo-sexual ; (2) a second category of rats that showed a range of two or three ejaculations and were considered as normal ejaculators; and (3) males who displayed four or ve ejaculations and were considered as rapid ejaculators or hypersexual rats The number of ejaculations across the various studies was distributed according to a Gaussian curve: on one side approximately 10% of rats display hypo-sexual behavior and on the other side 10% display hyper-sexual behavior after at least four successive weekly sexual tests of 30 min Interesting differences were found between the sluggish and rapid groups of rats with regard to a variety of other parameters of sexual behavior, resembling clinical symptoms of men suffering from retarded and premature ejaculation, respectively The hyper-sexual animals have been further investigated in order to know whether they could be used as a model for human premature ejaculation Compared to normal ejaculators, ejaculation
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1 sent during their early sexual experience For example, a sizable proportion (often nearly 50%) of male rats will not copulate during their rst trial with sexually receptive females unless they are pre-exposed to the testing chamber Indeed, a large proportion of these noncopulators will never copulate, despite repeated exposure to receptive females Novel environments are stressful to male rats, and induce the activation of endogenous opioids Treatment with the opioid antagonist naloxone can reverse this novelty-induced stress effect Another way to study hypoactive desire in male rats is to examine their sexual responsiveness following multiple ejaculations, a phenomenon known as sexual exhaustion Male rats are able to ejaculate several times before becoming unresponsive During this period of sexual activity, there is a progressive increase in the post-ejaculatory refractory period consonant, with a decrease in the number of intromissions before each ejaculation and a lengthening of the interintromission interval (a state that suggests a progressive loss of erectile function as the number of ejaculations increases) After males become sexually exhausted, they remain unresponsive to female solicitations for up to 72 hrs RodriguezManzo and colleagues have examined the ability of several classes of drug to increase the responsiveness of these males, including the opioid antagonist naloxone, 8-OH-DPAT, and the 2 presynaptic autoreceptor antagonist yohimbine Only yohimbine increased the proportion of males that mounted, intromitted, and displayed an ejaculatory-like behavioral pattern (but without seminal emission), suggesting that a decline in adrenergic activity is an important component of inhibited sexual desire in males
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latency was shorter in rapid ejaculators and longer in sluggish ejaculators Intromission and mount frequencies, the latter being considered as a putative index of sexual motivation, did not differ between the three categories of ejaculators, suggesting no differences in appetitive components of sexual behavior When investigating the effects of 8-hydroxy2-di-n-propylamino-tetralin (8-OH-DPAT) in these three categories of males, this compound was shown to induce a statistically signi cant increase in the number of ejaculations displayed by sluggish and normal rats, and to decrease in a statistically signi cant way the ejaculation latency in the sluggish , normal and rapid rats This experimental paradigm, despite the fact it has been recently reported and not yet con rmed by others, appears as extremely attractive Indeed hyper-sexual rats likely represent a pathophysiologic model of premature ejaculation It remains to be seen whether drugs that can counteract premature ejaculation in men can increase the latency of male rats to ejaculate in this condition It also remains to be studied whether such males are uniquely susceptible to an enforced interval effect
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