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E M Hull

Publications and source records attributed to E M Hull.

At least 55 records · Page 3Linked to original sources

Quinelorane (LY163502), a D2 dopamine receptor agonist, facilitates seminal emission, but inhibits penile erection in the rat.

Dopaminergic compounds have been shown to facilitate male sexual responses in various contexts. We investigated the effects of a specific D2 dopamine receptor agonist, quinelorane (LY163502), on sexual responses elicited in the restrained supine male rat (i.e., ex copula reflex tests). Penile erections, evoked by retraction of the penile sheath, were inhibited by systemic administration of 10 micrograms/kg quinelorane; however, the occurrence of seminal emission was dramatically increased. A smaller dose of 0.25 ng/kg was without effect. In a second experiment, intracranial microinjection of quinelorane was followed by ex copula reflex tests. The medial preoptic area (MPOA) has been previously implicated in the dopaminergic regulation of male copulatory behavior. The effects of an intra-MPOA injection of quinelorane on seminal emission and erectile responses were similar to those observed following systemic administration. These results are consistent with the hypothesis that DA receptors in the MPOA are important in the regulation of male sexual behavior and suggest that D2 receptors in the MPOA may decrease ejaculatory threshold while inhibiting erectile mechanisms.

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D2/D1 ratio in the medial preoptic area affects copulation of male rats.

The D1/D2 dopamine agonist apomorphine, microinjected into the medial preoptic area (MPOA), facilitates male rat sexual behavior and the D1/D2 antagonist cis-flupenthixol in the MPOA impairs it. The present study investigated the roles of D1 and D2 receptors in the regulation of copulation by microinjecting drugs selective for these receptors into the MPOA. The D2 agonist LY-163502 delayed the onset and slowed the rate of copulation and also reduced the number of vaginal intromissions required to trigger ejaculation (reduced ejaculatory threshold). The D1 agonist SKF-82526 had no effect, either alone or together with LY-163502. The D1 antagonist SCH-23390 delayed the onset of copulation and decreased ejaculatory threshold, as had the D2 agonist. A low dose of the D2 agonist alone and together with the D1 antagonist delayed the onset of copulation and reduced ejaculatory threshold; the combination of drugs was more effective than LY-163502 alone. Only the combination of drugs slowed the rate of copulation and delayed the resumption of copulation after an ejaculation. Thus, increasing the D2/D1 ratio in the MPOA, by selective stimulation of D2 and/or antagonism of D1 receptors, delays the onset of copulation and reduces ejaculatory threshold, possibly by altering autonomic control of penile reflexes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Microinjection of cis-flupenthixol, a dopamine antagonist, into the medial preoptic area impairs sexual behavior of male rats.

Systemically administered dopamine agonists have been shown to facilitate copulation in male rats. Microinjection of the dopamine agonist apomorphine into the medial preoptic area has also been reported to facilitate sexual behavior. The present experiments investigated the effects of medial preoptic microinjections of the dopamine antagonist cis-flupenthixol on male rat copulatory behavior. Fewer males initiated copulation and fewer ejaculated following flupenthixol administration. Those males that did ejaculate following flupenthixol injections had fewer ejaculations and longer interintromission intervals. Flupenthixol also antagonized the facilitative effects of apomorphine injections into the medial preoptic area. Flupenthixol and apomorphine produced only minor alterations in noncopulatory behaviors. The results suggest that dopamine receptors within the medial preoptic area are important in the regulation of masculine sexual behavior in the rat.

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Brain localization of cholinergic influence on male sex behavior in rats: agonists.

Cholinergic agonists were microinjected into either the lateral ventricle or the preoptic area of sexually experienced male rats. In Experiment 1 carbachol, injected into the lateral ventricles, delayed the initiation of sexual behavior. When injected into the preoptic area, carbachol again delayed the onset of copulation, but these delays were shorter than after ventricular injections. In addition, preoptic injections reduced the number of intromissions preceding ejaculation. In Experiment 2 ventricular injections of the muscarinic agonist oxotremorine again delayed initiation of sexual behavior and also slowed its rate. However, oxotremorine injections into the preoptic area, through cannulae angled to miss all ventricles, only decreased the number of intromissions preceding ejaculation. These data suggest that cholinergic synapses in proximity to the ventricles may decrease sexual arousal, while cholinergic mechanisms in or near the preoptic area may reduce ejaculatory threshold.

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Brain localization of cholinergic influence on male sex behavior in rats: antagonists.

The muscarinic receptor antagonist scopolamine was microinjected into either the preoptic area or the lateral ventricle, preceding sexual behavior tests. In Experiment 1 unilateral ventricular injections of scopolamine delayed the initiation of copulation, while unilateral preoptic injections had no effect. In Experiment 2 bilateral injections into the preoptic area produced dose-related decreases in the percentages of animals intromitting and ejaculating. In Experiment 3 scopolamine, injected alone into the preoptic area, again decreased the percentages of animals mounting, intromitting, and ejaculating. The muscarinic agonist oxotremorine, injected alone into the preoptic area, decreased ejaculatory threshold (i.e., decreased the number of intromissions preceding ejaculation) as previously reported. Concurrent oxotremorine and scopolamine injections into the preoptic area were not different from vehicle; thus, scopolamine blocked oxotremorine's effect. These data suggest that some cholinergic activation of the preoptic area is critical for normal copulation, since bilateral blockade of muscarinic receptors there dramatically decreased the number of animals copulating. However, increased cholinergic activity there only reduced ejaculation threshold.

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Apomorphine and haloperidol, but not domperidone, affect penile reflexes in rats.

Previous studies have shown that systemic administration of the dopamine agonist apomorphine produced a biphasic effect on erection in the freely moving rat, with lower doses facilitating, and high doses inhibiting, erection. However, those studies did not distinguish between erection per se and seminal emission. The present results demonstrate that apomorphine produces a similar biphasic effect on penile reflexes in the restrained, supine rat, while facilitating seminal emission in a monophasic fashion. Haloperidol, a centrally-acting dopamine antagonist, either blocked the effects produced by apomorphine administration, or had actions opposite to those of apomorphine. Domperidone, a dopamine antagonist that does not readily penetrate the blood-brain barrier, did not antagonize apomorphine's effects, and did not affect penile responses when administered alone. These results suggest that dopamine receptors in the central nervous system regulate genital responses, and that effects on penile reflexes and seminal emission can be experimentally dissociated.

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Regulation of male rat copulatory behavior by preoptic incertohypothalamic dopamine neurons.

The role of dopaminergic terminals in the medial preoptic area (MPO) in the regulation of male rat copulatory behavior was investigated. A 6-hydroxydopamine (6-OHDA) injection into the MPO of animals pretreated with desipramine resulted in a small (23%) depletion of DA, and no impairment of copulatory activity. Further depletion of catecholamines with alpha-methyl p-tyrosine (AMPT) produced several deficits in the copulatory behavior of 6-OHDA-treated males, at a dose of AMPT that did not adversely affect copulation prior to 6-OHDA administration. The dose-related effects of intracranial apomorphine (APO) injections were also altered by 6-OHDA injections into the MPO. The inhibition previously found with 0.2 microgram of APO into the lateral ventricle of normal males was abolished by 6-OHDA treatment. A facilitation of copulatory behavior was observed following the injection of 0.2 microgram of APO into the MPO of 6-OHDA-treated animals, whereas this treatment did not affect the copulatory behavior of intact animals. Finally, inhibitory effects observed following an injection of 0.1 microgram of APO into the MPO of normal males were blocked by 6-OHDA administration. The relative roles of presynaptic autoreceptors and postsynaptic DA receptors in the MPO in mediating the dose-related effects of APO on copulatory behavior are discussed.

3,4-Dihydroxyphenylacetic Acid↗

Pharmacological analysis of male rat sexual behavior.

Pharmacological influences on male rat sexual behavior are reviewed in an attempt to identify neurotransmitters and their respective receptor types that regulate various factors comprising the behavioral pattern. Evidence is presented that: (1) serotonergic influence is generally inhibitory to sexual behavior, although two receptor subtypes may lower ejaculation threshold; (2) dopaminergic agonists facilitate several aspects of copulatory behavior and ex copula genital responses; (3) noradrenergic activity appears to increase sexual arousal; (4) cholinergic agonists facilitate ejaculation, or in some cases, delay or prevent initiation of copulation; (5) GABA agonists inhibit sexual responses both in and ex copula; (6) opiate agonists appear to inhibit copulation and penile reflexes, although antagonists have mixed effects; (7) ACTH and MSH peptides promote copulatory behavior and genital responses; (8) oxytocin facilitates ex copula penile responses, but may contribute to postejaculatory refractoriness; and (9) long-term exposure to prolactin inhibits sexual behavior and penile responses. Although some progress has been made in identifying neurotransmitter-receptor effects on behavioral components, copulatory behavior is complex and no drug has been found to affect only a single component. Furthermore, drug specificity is only relative.

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Dopaminergic control of male sex behavior in rats: effects of an intracerebrally-infused agonist.

Systemically-administered dopaminergic drugs have been found to facilitate sexual behavior of men and male rats. The present experiments investigated the localization within the brain of dopaminergic effects on copulation of male rats. Apomorphine, a dopamine agonist, was microinfused into the medial preoptic area, caudate-putamen, nucleus accumbens, lateral septum and lateral ventricle. The lowest dose of apomorphine (0.2 microgram) infused into the ventricle reduced the number of ejaculations, slowed the rate of intromitting and decreased the percentage of mounts on which the male gained vaginal intromission. The higher two doses (0.5 and 2.0 micrograms) infused into the medial preoptic area and, in some cases, the ventricle, increased the number of ejaculations and the percentage of mounts with vaginal intromission, increased the rate of intromitting and decreased the latency to ejaculate and the postejaculatory interval before resuming copulation. Infusions into the caudate-putamen and lateral septum were without effect. Those into nucleus accumbens produced only a slight dose-related decrease in latency to begin copulating. The copulatory impairments associated with infusions of the lowest dose into the ventricle may have resulted from stimulation of autoreceptors, or from preferential stimulation by low doses of an undetermined area. The facilitative effects of the two higher doses into the medial preoptic area and lateral ventricle may have been due to stimulation of dopaminergic postsynaptic receptors.

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Perinatal dopamine-related drugs demasculinize rats.

Administration of haloperidol, a common neuroleptic, to pregnant or lactating rats impaired the masculine sex behavior of their male offspring. Prenatal haloperidol did not affect testosterone concentrations in fetuses. Maternal administration of apomorphine, a dopamine agonist, and of alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, also demasculinized male offspring. In both experiments other behaviors and developmental milestones were unaffected. Perinatal haloperidol, apomorphine, and alpha-methyl-p-tyrosine did not lower testosterone in adulthood. These drugs may act directly on neurons that control masculine behavior without lowering testosterone prenatally or in adulthood.

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