Neuroendocrine regulatory peptide-1 and neuroendocrine regulatory peptide-2 influence differentially feeding and penile erection in male rats: sites of action in the brain.

The effect of NERP-1 and NERP-2, two recently discovered VGF-derived peptides, on feeding and penile erection was studied after injection into the lateral ventricles, the lateral hypothalamus, the arcuate nucleus or the paraventricular nucleus of the hypothalamus. NERP-2 (1-5 nmol), but not NERP-1 (2-4 nmol), increased feeding in a dose-dependent manner when injected into the lateral ventricles or bilaterally into the lateral hypothalamus but not into the arcuate or the paraventricular nucleus. The effect of NERP-2 given into the lateral ventricles was found in the first, but not in the second 60 min after treatment, and was antagonized by SB-408124, an orexin-1 receptor antagonist given into the lateral ventricles or the arcuate nucleus, but not into the paraventricular nucleus.

Dopamine agonist-induced penile erection and yawning: differential role of D₂-like receptor subtypes and correlation with nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats.

The dopamine D₃ preferring agonist pramipexole (50 ng) induced penile erection and yawning when injected into the paraventricular nucleus of the hypothalamus of male rats, like the mixed D₁/D₂-like agonist apomorphine (50 ng), while the D₄ agonist PD 168,077 (100 ng), induced penile erection only. These responses lasted for 45-60 min and occurred with an increase of NO₂- and NO₃- concentrations in the dialysate obtained from the paraventricular nucleus by intracerebral microdialysis. Pramipexole and apomorphine responses were reduced by the D₂ preferring antagonist L-741,626 (5 μg), but not by the D₃ preferring antagonist SB-277011A (10 μg), or the D₄ preferring antagonist L-745,870 (5 μg), injected into the PVN before the dopamine agonist.

Dopamine D2-like receptor agonists induce penile erection in male rats: differential role of D2, D3 and D4 receptors in the paraventricular nucleus of the hypothalamus.

Pramipexole, a dopamine D3/D2 receptor agonist, induces penile erection when administered subcutaneously (s.c.) or into the paraventricular nucleus of the hypothalamus of male rats, like apomorphine, a mixed D1/D2 receptor agonist, and PD 168,077, a D4 receptor agonist.

Oxytocin injected into the hippocampal ventral subiculum induces penile erection in male rats by increasing glutamatergic neurotransmission in the ventral tegmental area.

Oxytocin (100 ng) injected unilaterally into the ventral subiculum of the hippocampus induces penile erection episodes, which started 30 min after treatment and were abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (2 μg), an oxytocin receptor antagonist, into the ventral subiculum. Oxytocin-induced penile erection occurred 15 min after the increase of the concentration of extracellular dopamine in the dialysate obtained from either the nucleus accumbens or the prelimbic medial prefrontal cortex, which was also abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin. An increase in extracellular glutamic acid concentration was also observed in the same dialysate obtained from the ventral tegmental area, but not from the prelimbic medial prefrontal cortex or the nucleus accumbens in which dopamine concentration was measured, 15 min after the injection of oxytocin into the ventral subiculum.

Oxytocin induces penile erection when injected into the ventral subiculum: role of nitric oxide and glutamic acid.

Oxytocin (100 ng) induces penile erection when injected unilaterally into the ventral subiculum of the hippocampus of male rats. The pro-erectile effect started mostly 30 min after treatment and occurred 15 min after an increase in both nitric oxide (NO) production, measured by the concentration of NO(2)(-) and NO(3)(-), the main metabolites of newly formed NO, and extra-cellular glutamic acid concentration in the dialysate obtained from the ventral subiculum by intracerebral microdialysis. These responses were abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (2 microg), an oxytocin receptor antagonist, S-methyl-L-thiocitrulline (SMTC), a selective inhibitor of neuronal NO-synthase (25 microg), and haemoglobin, a NO scavenger (25 microg), given into the ventral subiculum before oxytocin.

Oxytocin injected into the ventral subiculum or the posteromedial cortical nucleus of the amygdala induces penile erection and increases extracellular dopamine levels in the nucleus accumbens of male rats.

Oxytocin (20-100 ng) was found to be able to induce penile erection when injected unilaterally into the ventral subiculum or the posteromedial cortical nucleus of the amygdala of male rats. The pro-erectile effect started mostly 30 min after treatment and was abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (1-2 microg), an oxytocin receptor antagonist, into the ventral subiculum or posteromedial cortical nucleus. Oxytocin-induced penile erection occurred 15 min after the increase in the concentration of extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the dialysate obtained from the nucleus accumbens, which was also abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin.

Phosphodiesterase type 5 inhibitors facilitate noncontact erections in male rats: site of action in the brain and mechanism of action.

Introduction: Orally active phosphodiesterase type 5 inhibitors (PDE5i), used in the treatment of erectile dysfunction, facilitate the relaxation of cavernous smooth muscle tissues by reducing the degradation of cyclic guanosine monophosphate.

Aims: The aims of this article were to determine whether PDE5i facilitate penile erection and male sexual behavior by acting also on the central nervous system and to investigate their mechanism of action at central level.

Methods: PDE5i (sildenafil, vardenafil, and tadalafil) given intraperitoneally (i.

Oxytocin induces penile erection when injected into the ventral tegmental area of male rats: role of nitric oxide and cyclic GMP.

Oxytocin (80 ng) injected into the caudal mesencephalic ventral tegmental area (VTA) of male rats induces penile erection. Such an effect occurs together with an increase in nitric oxide (NO) production, as measured by the augmented concentration of NO(2)(-) and NO(3)(-) found in the dialysate obtained from this brain area by means of intracerebral microdialysis. Both effects are abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), an oxytocin receptor antagonist, by S-methyl-l-thiocitrulline acetate (20 microg), a neuronal NO synthase inhibitor, or by omega-conotoxin GVIA (50 ng), a N-type Ca(2+) channel blocker, all injected into the VTA 15 min before oxytocin.

Oxytocin injected into the ventral tegmental area induces penile erection and increases extracellular dopamine in the nucleus accumbens and paraventricular nucleus of the hypothalamus of male rats.

The neuropeptide oxytocin (20-100 ng), induces penile erection when injected unilaterally into the caudal but not rostral mesencephalic ventral tegmental area (VTA) of male Sprague-Dawley rats. Such pro-erectile effect started 30 min after treatment and was abolished by the prior injection of d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), an oxytocin receptor antagonist injected into the same caudal ventral tegmental area or of haloperidol (1 microg), a dopamine receptor antagonist, injected either into the nucleus accumbens shell (NAs) or into the paraventricular nucleus of the hypothalamus (PVN) ipsilateral to the injected ventral tegmental area. Penile erection was seen 15 min after the occurrence of, or concomitantly to, an increase in extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate obtained from the nucleus accumbens or the paraventricular nucleus, which was also abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), injected into the ventral tegmental area before oxytocin.

The cannabinoid antagonist SR 141716A (Rimonabant) reduces the increase of extra-cellular dopamine release in the rat nucleus accumbens induced by a novel high palatable food.

The assumption of a novel high palatable food (a candied cherry) occurs concomitantly with an increase in the concentration of extra-cellular dopamine and its main metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC) by about 45% in the dialysate obtained by intracerebral microdialysis from the shell of the nucleus accumbens of male rats. Such increase was reversed by SR 141716A (Rimonabant), a selective cannabinoid CB1 receptor antagonist (0.3 mg/kg i.

Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: Involvement of central oxytocin.

The effect of a pro-erectile dose of apomorphine, a mixed dopamine receptor agonist, and of PD-168077 (N-[4-(2-cyanophenyl)piperazin-1-ylmethyl]-3-methylbenzamide maleate), a selective dopamine D4 receptor agonist, injected into the paraventricular nucleus of the hypothalamus on the concentration of extra-cellular dopamine and its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate from the nucleus accumbens was studied in male rats. As expected, apomorphine (0.1microg) and PD-168077 (0.

PIP3EA and PD-168077, two selective dopamine D4 receptor agonists, induce penile erection in male rats: site and mechanism of action in the brain.

PIP3EA (2-[4-(2-methoxyphenyl)piperazin-1-yl-methyl]imidazo[1,2-a]pyridine) and PD-168077 (N-[4-2-cyanophenylpiperazin-1-ylmethyl]-3-methylbenzamide maleate), two selective dopamine D4 agonists, administered systemically, intracerebroventricularly or into the paraventricular nucleus of the hypothalamus induce penile erection in male Sprague-Dawley rats. A U-inverted dose-response curve was found with either compound when given subcutaneously (1-100 microg/kg) or intracerebroventricularly (0.1-20 microg/rat), but not into the paraventricular nucleus (10-200 ng/rat).

Morphine reduces penile erection induced by the cannabinoid receptor antagonist SR 141617A in male rats: role of paraventricular glutamic acid and nitric oxide.

The effect of the opiate morphine, on penile erection induced by the cannabinoid CB1 receptor antagonist SR 141716A injected into the paraventricular nucleus of the hypothalamus and on the increase in the concentration of glutamic acid and of NO(2)(-) and NO(3)(-), which occurs concomitantly in the paraventricular dialysate obtained by intracerebral microdialysis, was studied in male rats. Morphine (0.5, 1 and 5 microg), given into the paraventricular nucleus, reduced dose-dependently penile erection induced by SR 141716A (2 microg) injected into the paraventricular nucleus.

The cannabinoid CB1 receptor antagonist SR 141716A induces penile erection by increasing extra-cellular glutamic acid in the paraventricular nucleus of male rats.

The cannabinoid CB1 receptor antagonist SR 141716A (0.1, 0.5 and 1 microg) induces penile erection when injected into the paraventricular nucleus of the hypothalamus of male rats.

The cannabinoid receptor antagonist SR-141716A induces penile erection in male rats: involvement of paraventricular glutamic acid and nitric oxide.

The cannabinoid CB1 receptor antagonist SR141716A (0.5, 1 and 2 microg) induces penile erection when injected into the paraventricular nucleus of male rats. The pro-erectile effect of SR 141716A occurs concomitantly with an increase in the concentration of NO2- and NO3- in the paraventricular dialysate obtained by means of intracerebral microdialysis.

Pro-VGF-derived peptides induce penile erection in male rats: Involvement of paraventricular nitric oxide.

The effect of four peptides derived from the C-terminal portion of rat pro-VGF(556-617) (VGF(556-576), VGF(588-617), VGF(599-617), and VGF(588-597)), on penile erection and nitric oxide production in the paraventricular nucleus of the hypothalamus was studied in male rats after injecting into this hypothalamic nucleus. VGF(588-617) (0.5, 1 and 2 microg), VGF(599-617) (0.

PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats.

The effect of PD-168077 (N-methyl-4-(2-cyanophenyl)piperazynil-3-methylbenzamide maleate), a selective D4 dopamine receptor agonist, injected into the paraventricular nucleus of the hypothalamus on penile erection was studied in male rats. PD-168077 (1-200 ng) induced penile erection in a dose-dependent manner. The minimal effective dose was 50 ng, while the maximal response was found with 200 ng of the compound, which increased penile erection episodes from 0.

Pro-VGF-derived peptides induce penile erection in male rats: possible involvement of oxytocin.

The effect of five peptides derived from the C-terminal portion of rat pro-VGF (VGF(577-617), VGF(588-617), VGF(599-617), VGF(556-576) and VGF(588-597)) on penile erection was studied after injection into the hypothalamic paraventricular nucleus of male rats. VGF(577-617), VGF(588-617), VGF(599-617) and, to a lower extent, VGF(588-597) (0.1-2 microg) induced penile erection episodes in a dose-dependent manner when injected into the paraventricular nucleus, while VGF(556-576) was ineffective.

Extracellular excitatory amino acids increase in the paraventricular nucleus of male rats during sexual activity: main role of N-methyl-d-aspartic acid receptors in erectile function.

The concentrations of glutamic and aspartic acids were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats during sexual activity. Animals showed noncontact erections when put in the presence of, and copulated with, a receptive (ovarietomized oestrogen- and progesterone-primed) female rat. The concentrations of glutamic and aspartic acids in the paraventricular dialysate increased by 37 and 80%, respectively, above baseline values during exposure to the receptive female rat and by 55 and 127%, respectively, during copulation.

Antagonism of cannabinoid CB1 receptors in the paraventricular nucleus of male rats induces penile erection.

The effect of cannabinoid CB1 receptor agonists and antagonists on penile erection was studied in male rats when injected into the paraventricular nucleus of the hypothalamus. The CB1 receptor antagonist SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (0.5-5 microg) induced penile erection in a dose-dependent manner.

Activation of GABAA and opioid receptors reduce penile erection induced by hexarelin peptides.

The effect of muscimol, a GABA(A) receptor agonist, and of morphine, an opioid receptor agonist, on penile erection induced by the hexarelin analogue peptide EP 80661 (GAB-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2)) and on the increase in the concentration of NO(2)(-) and NO(3)(-) that occurs concomitantly in the dialysate obtained from the paraventricular nucleus (PVN) of the hypothalamus by intracerebral microdialysis, was studied in male rats. Muscimol (50, 100 and 200 ng) and morphine (0.1, 0.

Extra-cellular dopamine increases in the paraventricular nucleus of male rats during sexual activity.

Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats. Animals showed noncontact erections when put in the presence of, and copulated with a receptive (ovarietomized oestrogen and progesterone primed) female rat. Dopamine and DOPAC concentrations in the paraventricular dialysate increased 140% and 19%, respectively, above baseline values during exposure to the receptive female and 280% and 31%, respectively, during copulation.

Ghrelin injected into the paraventricular nucleus of the hypothalamus of male rats induces feeding but not penile erection.

The effect of ghrelin, a recently characterized endogenous receptor agonist for growth hormone (GH) secretagogue receptors, on feeding and penile erection was compared with that of EP 80661, a peptide analogue of the GH secretagogue hexarelin, previously identified for its pro-erectile activity when injected into the paraventricular nucleus of the hypothalamus of male rats. Ghrelin (0.01-1 microg), but not EP 80661 (0.