Biomedical subjects

E M Hull

Publications and source records attributed to E M Hull.

At least 37 records · Page 2Linked to original sources

PubMed1995

Cholecystokinin modulates mesolimbic dopaminergic influences on male rat copulatory behavior.

Much evidence suggests that the neuropeptide cholecystokinin (CCK) functions as a neurotransmitter or neuromodulator in the central nervous system. The CCKa receptor subtype in the nucleus accumbens has been demonstrated to potentiate the behavioral and neurophysiological effects of dopamine. Since the mesolimbic dopamine system participates in the regulation of male rat sexual behavior, the present investigation was undertaken to determine if central CCK modulates this dopaminergic regulation. Electrical stimulation of the ventral tegmental area greatly enhanced several measures of appetitive and consummatory male rat sexual behavior. Administration of a CCKa receptor antagonist to the posteromedian nucleus accumbens reversed the electrically stimulated behavioral enhancement. A CCKb antagonist was without effect. In a second group of animals, administration of either a CCKa or CCKb antagonist to the anterolateral nucleus accumbens reversed the enhancement of consummatory sexual responding produced by electrical stimulation. These results agree with the growing body of evidence supporting different behavioral roles for two distinct CCK systems in the nucleus accumbens.

Animals↗

PubMed1995

Effects of morphiceptin in the medial preoptic area on male sexual behavior.

Morphiceptin, a selective mu opioid agonist, injected into the medial preoptic area (MPOA), delayed the onset of copulation in male rats, but did not affect genital reflexes, sexual motivation or general motor activity. In a dose-dependent manner, morphiceptin (100 ng and 1000 ng) injected into the MPOA increased mount and intromission latencies. Similar injections of morphiceptin into the ventromedial hypothalamus had no effect on any parameter of copulation. The increase in copulatory latencies following the injection of the highest dose of morphiceptin was blocked by pretreatment with the opioid antagonist naloxone. In the X-maze task, morphiceptin had no effect on sexual motivation, as measured by the percentage of trials on which the male chose the female's chamber, but it increased the number of trials in which the subject did not select a chamber within 60 s and the latency to the female the first time he chose her chamber. Similar to the copulation task, the mount and intromission latencies were also increased in the X-maze, after the male reached the female. Morphiceptin in the MPOA had no effect on ex copula genital reflexes, tested in restrained supine males, or on motor activity, tested in a grid box. These results suggest that morphiceptin disrupts either the specific copulatory somatomotor pattern or a more general motivational component.

Analgesics↗

PubMed1995

Dopaminergic drugs in the medial preoptic area and nucleus accumbens: effects on motor activity, sexual motivation, and sexual performance.

In two experiments, dopamine agonists and/or antagonists were injected into the medial preoptic area (MPOA) or the nucleus accumbens (NAcc) of male rats. The animals were then tested in an X-mase with four goal boxes, which contained a receptive female, a male, or were empty. In Experiment 1, the D1 antagonist SCH-23390 and the D2 antagonist raclopride in the MPOA decreased the percentage of trials on which the female's chamber was chosen, a measure of sexual motivation. Raclopride also decreased the number of animals that copulated after choosing the female's chamber. The 10-micrograms dose of the D3/D2 agonist quinelorane increased the latency to reach the female's chamber, slowed the onset of copulation, and decreased the number of intromissions preceding an ejaculation. In Experiment 2, 1- and 5-micrograms doses of quinelorane and of the mixed D1/D2 agonist apomorphine were injected bilaterally into the NAcc. Both doses of quinelorane increased the number of times that the subject did not select a chamber within 60 s. No drug in the NAcc affected specifically sexual motivation or performance. The results are consistent with differential influence of the MPOA and the NAcc on motor activity, sexual motivation, and sexual performance.

Animals↗

PubMed1995

Extracellular dopamine in the medial preoptic area: implications for sexual motivation and hormonal control of copulation.

Dopamine (DA) activity in the medial preoptic area (MPOA) contributes to the control of male rat sexual behavior. We tested (1) whether extracellular DA increases during precopulatory exposure to an estrous female and during copulation, (2) whether exposure to another male increases extracellular DA, (3) whether motor activity during copulation accounts for increased DA levels, and (4) whether concurrent or recent testosterone influences DA levels or copulation in castrates. Extracellular DA and its metabolites in male rats' MPOA were measured using microdialysis. DA level increased during precopulatory exposure to the female in all animals that subsequently copulated; this included all intact animals, all testosterone-treated castrates, and 9 of 14 1-week castrates treated with oil vehicle. DA levels did not increase in any animal that subsequently failed to copulate, including the remaining 1-week, and all 2-week, vehicle-treated castrates. When the barrier was removed and the animals were allowed to copulate, levels of DA and its metabolites continued to rise in intact males and in castrates that copulated. The DA response to the estrous female could not be attributed to nonsexual social stimuli, since exposure to another male was ineffective. The DA response to copulation could not be attributed primarily to motor activity, since animals running voluntarily in a running wheel did not show significantly increased DA. These and previous data suggest that DA released in the MPOA in response to an estrous female may contribute to sexual motivation and copulatory proficiency. Testosterone may promote copulation in part through permissive actions on dopamine release.

Animals↗

PubMed1994

The roles of nitric oxide in sexual function of male rats.

Nitric oxide (NO) may mediate penile erection by inhibiting smooth muscle of the corpora cavernosa, thereby allowing vasodilation of the corpora. In order to test the role of NO in the sexual function of intact male rats, either the precursor of NO (L-arginine, L-Arg) or an inhibitor of its synthesis (NG-nitro-L-arginine methyl ester, NAME) was administered systemically before tests of copulation, ex copula genital reflexes, or sexual motivation/motor activity. NAME impaired copulation in a dose dependent manner. It also decreased the number of ex copula erections, but it increased the number of ex copula seminal emissions and decreased the latency to the first seminal emission. L-Arg marginally increased the number of penile reflexes, but had no other effects. NAME had no effect on sexual motivation or motor activity. The results indicate that nitric oxide promotes erection in intact male rats, probably by mediating filling of the corpora cavernosa. The data also suggest that NO inhibits seminal emission, probably by decreasing sympathetic nervous system activity; this may help prevent premature ejaculation.

Amino Acid Oxidoreductases↗

PubMed1994

A D1 agonist in the MPOA facilitates copulation in male rats.

The classic dopamine agonist apomorphine, microinjected into the medial preoptic area (MPOA), enhances the copulatory behavior of male rats, while pharmacological blockade of endogenous dopamine inhibits sexual behavior. We now report that MPOA injections of 10 micrograms of the selective D1 agonist dihydroxyphenyl-tetrahydrothienopyridine (THP) significantly increased the number of ejaculations, while decreasing the latency to ejaculate in a 30-min test. These effects were not observed following coadministration of the selective D1 antagonist SCH-23390 with 10 micrograms THP. This enhancement may be related to a D1-stimulated facilitation of penile erections.

Animals↗

PubMed1993

Nitric oxide increases dopamine and serotonin release in the medial preoptic area.

Nitric oxide (NO) is becoming recognized as an important intercellular messenger in the brain. The present experiment used microdialysis to examine the potential role of NO in the regulation of dopamine (DA) and serotonin (5-HT) release in the medial preoptic area (MPOA) of freely moving male rats. The NO precursor L-arginine (L-Arg, 100 microM), administered into the MPOA via the dialysis probe, increased extracellular levels of DA, 5-HT, and the major metabolites of DA. These increases were blocked by the coadministration of the NO synthase inhibitor N-monomethyl L-arginine (NMMA, 400 microM). The inactive isomer D-arginine (100 microM) was ineffective, and NMMA by itself decreased DA below baseline levels. Thus, NO may modulate the release of DA and 5-HT in the MPOA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Copulation increases dopamine activity in the medial preoptic area of male rats.

Dopamine (DA) metabolites in microdialysates from the medial preoptic area (MPOA) of male rats increased during copulation. These increases were not observed during eating of a highly palatable food, or if the animal failed to copulate, or if the microdialysis probe was anterior or dorsal to the MPOA. The only two animals with measurable serotonin (5-HT) levels while the female was present were also the only two that either failed to copulate or copulated but failed to ejaculate. These data are consistent with previous evidence for a facilitative role of MPOA DA in the control of male sexual behavior; however, 5-HT activity in the MPOA may impair copulation.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation.

Dopamine D1 and D2 receptors may synergize with or oppose each other's effects. We suggest that stimulation of D1 and D2 receptors in the medial preoptic area (MPOA) of male rats have opposing effects on genital reflexes. In Experiment 1 a D1 agonist injected into the MPOA increased the number of ex copula erections but decreased the number of seminal emissions. In Experiment 2 a D1 antagonist had the opposite effects (decreased erections and increased seminal emissions), as had a D2 agonist previously. We also suggest that D1 and D2 mechanisms in the MPOA have different thresholds of activation. In Experiment 3 a low dose of the mixed D1/D2 agonist apomorphine increased erections and anteroflexions, an effect blocked by the D1 antagonist. In Experiments 3 and 4 a high dose of apomorphine increased seminal emissions, an effect blocked by the D2 antagonist. Thus, low levels of dopaminergic stimulation may facilitate erections and anteroflexions (controlled by the parasympathetic system and striated muscles) via D1 receptors; higher or more prolonged stimulation may shift to seminal emission (controlled by the sympathetic system) via D2 receptors. This may explain the progression from erectile to ejaculatory mechanisms during copulation.

Animals↗

PubMed1991

Dopamine receptors in the ventral tegmental area affect motor, but not motivational or reflexive, components of copulation in male rats.

Microinjection of apomorphine into the ventral tegmental area (VTA) of male rats was previously shown to delay the onset of copulation and slow its rate, presumably by stimulating impulse-regulating autoreceptors on cell bodies of the A10 mesocorticolimbic dopamine tract. Such stimulation would be expected to slow the firing rate of these neurons and, thereby, to impair locomotion and/or motivational processes. The present experiments tested whether the delayed onset and slowed rate of copulation were related to deficits in motor performance, sexual motivation, and/or genital reflexes. In X-maze tests the speed of running to all 4 goal boxes was slowed; however, the percentage of trials on which the male chose the female's goal box was not decreased. Examination of videotaped copulation tests revealed that the male showed fewer complete copulatory behaviors (mounts, intromissions, and ejaculations), but more misdirected or incomplete copulatory attempts after apomorphine in the VTA. There were also fewer scores of active, as opposed to inactive, behaviors, and the onset and rate of copulation were slowed. The total number of female directed behaviors was not different in apomorphine tests, compared to vehicle. Finally, tests of ex copula genital reflexes revealed no significant effects of apomorphine in the VTA on erections, penile movements, or seminal emissions. These data suggest a role of the VTA in the motor aspects and/or sensorimotor integration of copulation. Sexual motivation and ex copula genital reflexes appeared to be unaffected by apomorphine in the VTA.

Animals↗

PubMed1991

Microinjection of the dopamine antagonist cis-flupenthixol into the MPOA impairs copulation, penile reflexes and sexual motivation in male rats.

Microinjection of the dopamine antagonist cis-flupenthixol into the medial preoptic area was previously shown to impair male rat copulatory behavior. The present experiments provide further evidence of cis-flupenthixol's inhibitory effects on male sexual behavior. Following microinjections of moderate to high doses of cis-flupenthixol, males exhibited slower copulatory rates and fewer ejaculations in copula, fewer ex copula erections and penile movements, and reduced sexual motivation in an X-maze. Locomotion in the X-maze was not significantly affected. Microinjections of the inactive isomer trans-flupenthixol produced no change in any behavioral measure, indicating that cis-flupenthixol's effects were receptor mediated. We suggest that dopamine receptors in the MPOA influence copulation primarily by regulating reflexive and motivational factors, but not locomotion.

Animals↗

PubMed1991

Dose dependent D2 effects on genital reflexes after MPOA injections of quinelorane and apomorphine.

This study investigated the effects on genital reflexes of unilateral MPOA injections of 0.1, 1, 3, and 10 micrograms of the D2 agonist quinelorane (LY-163502), and of 3 micrograms quinelorane administered together with 3 micrograms of the D1 antagonist SCH-23390. In addition, the effects of an MPOA injection of 10 micrograms apomorphine were tested. All but the lowest dose of quinelorane significantly decreased the latency to the first reflex. The 3 and 10 micrograms doses of quinelorane, and the combination of quinelorane and SCH-23390, decreased the total number of reflexes. In addition, 10 micrograms quinelorane increased the number of seminal emissions. 10 micrograms apomorphine, like 10 micrograms quinelorane, decreased the latency to the first reflex and increased the number of seminal emissions, but did not decrease the numbers of erections or penile movements. The ratio of D1/D2 activity may influence the number of erections displayed during ex copula testing.

Animals↗

PubMed1991

D2 receptors in the paraventricular nucleus regulate genital responses and copulation in male rats.

The D2 dopamine receptor agonist quinelorane (LY-163502), microinjected into the paraventricular nucleus (PVN), affected genital response of restrained supine male rats in a biphasic dose-dependent fashion. A moderate dose (1 microgram) facilitated penile responses (intense erections and penile movements), and decreased the latency to the first response. A high dose of quinelorane (10 micrograms) facilitated seminal emission while inhibiting penile responses. The addition of the D1 antagonist SCH-23390 to the 1 microgram dose of quinelorane potentiated quinelorane's increase in seminal emission. We suggest that D1 receptors in the PVN may be antagonistic to D2 receptor-mediated seminal emission, and possibly also penile responses. In copulation tests 1 microgram quinelorane decreased mount latency, whereas 10 micrograms quinelorane increased mount and intromission latencies and slowed copulatory rate. Both 1 and 10 micrograms quinelorane, and also 1 and 10 micrograms of the mixed D1 and D2 agonist apomorphine, decreased the number of intromissions preceding ejaculation.

Animals↗

PubMed1990

Morphine and dynorphin(1-13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats.

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01-6 nmol) and dynorphin(1-13) (0.01-3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10-100 pmol) and dynorphin (10-100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1-10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.

Animals↗

PubMed1990

Dopamine receptors in the ventral tegmental area modulate male sexual behavior in rats.

The mesocorticolimbic dopamine tract is considered to be a substrate for motivation and reward as well as for locomotor behavior. The present experiments assessed the role of dopamine cell bodies in the ventral tegmental area (VTA), the source of this tract, in the copulatory behavior of male rats. The dopamine agonist apomorphine or the dopamine antagonist cis-flupenthixol were microinjected into the VTA immediately before sexual behavior tests with a receptive female. Apomorphine delayed the onset of copulation and slowed its rate, presumably by stimulating somatodendritic autoreceptors and thereby decreasing the firing rate of VTA neurons. Control injections of apomorphine into the substantia nigra were without effect. cis-Flupenthixol, which would have blocked autoreceptors and thereby depolarized VTA neurons, shortened the latency to begin copulating in those animals that did copulate; however, fewer animals exhibited sexual behavior. One possible explanation for the apparently contradictory effects of cis-flupenthixol may be that VTA neurons increased their rate of firing in some animals, leading to a faster onset of copulation, but that in other animals depolarization block in a substantial number of neurons resulted in a lack of copulation. These results are consistent with a contribution of the mesocorticolimbic dopamine tract to motivational and/or motor aspects of male copulatory behavior.

Action Potentials↗

PubMed1990

Systemic or intracranial apomorphine increases copulation in long-term castrated male rats.

Testosterone or its estrogenic metabolite is thought to be necessary to activate male rat sexual behavior. However, systemic injections of dopamine agonists, alone or in combination with exogenous testosterone, can partially restore copulatory behavior during the prolonged period of its postcastration decline. The present experiments tested the ability of the dopamine agonist apomorphine, injected systemically or into the medial preoptic area (MPOA), to restore copulation in long-term castrates that had failed to copulate on two successive weekly tests. In Experiment 1, systemic injections of apomorphine increased the number of mounts and intromissions in castrated males, compared to vehicle. In castrates given subthreshold testosterone propionate (TP), apomorphine increased the number of mounts. In Experiment 2, microinjections of apomorphine into the MPOA increased the number of mounts in animals without TP. Subthreshold TP had no significant effects in either experiment, either alone or interacting with apomorphine. These results suggest that stimulation of dopamine receptors can partially restore copulation, even after its virtual elimination. Furthermore, dopamine receptors in the MPOA may contribute to sexual arousal in long-term castrates.

Animals↗

PubMed1989

The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat.

Previous studies employing systemic administration of the dopamine agonist apomorphine have shown that the dose response curves for apomorphine's effects on penile reflexes and seminal emission differ, suggesting that experimentally separable populations of dopamine receptors regulate these two responses. The present experiments examined the locations of central nervous system DA receptors mediating genital responses in the restrained, supine rate by injecting apomorphine into the medial preoptic area and the paraventricular nucleus through chronic, indwelling cannulae. Medial preoptic area injections facilitated penile reflexes, but not seminal emission, while paraventricular injections facilitated seminal emission. These results suggest that systemically administered apomorphine may facilitate penile reflexes by acting on the medial preoptic area and may enhance seminal emission by acting on the paraventricular nucleus.

Animals↗

PubMed1989

The effects of intrathecal administration of the dopamine agonist apomorphine on penile reflexes and copulation in the male rat.

Relatively high doses of systemically administered apomorphine inhibit penile reflexes. It is possible that these inhibitory effects are due, at least in part, to actions of apomorphine on the lumbosacral spinal cord. The present experiments examined this possibility by injecting apomorphine (10 and 50 micrograms/5.0 microliters vehicle) into the lumbosacral subarachnoid space through chronic, indwelling cannulae. Such injections impaired ex copula penile reflexes, slowed the rate of copulation, and decreased the number of intromissions preceding ejaculation. These results suggest that lumbosacral cord dopamine receptors may normally regulate male sexual performance.

Animals↗