Opioid-receptor-mediated inhibition of [3H]dopamine but not [3H]noradrenaline release from rat mediobasal hypothalamus slices.
ABSTRACT The modulation of the electrically evoked release of [3H]dopamine (DA) and [3H]noradrenaline (NA) by opioid receptor activation was examined in superfused slices of rat mediobasal hypothalamus (MBH). [3H]DA release was inhibited (maximally by 30-35%) by both the selective kappa-agonist U 50,488 (1 nM to 1 microM) and the selective mu-agonist DAGO (0.01-1 microM) but not by the delta-selective agonist DPDPE (1 microM). Naloxone partly antagonized the inhibitory effect of U 50,488 and completely that of DAGO, whereas the selective kappa-antagonist norbinaltorphimine (nor-BNI) only antagonized the inhibition caused by U 50,488. The dopamine D2 receptor agonist quinpirole as well as the alpha 2-adrenoceptor agonist oxymetazoline both decreased (by 25-30%) the evoked overflow of [3H]DA. The evoked release of [3H]NA was not modulated by any of the opioid agonists nor by quinpirole. However, the alpha 2-adrenoceptor agonist oxymetazoline inhibited the release of [3H]NA by 30-40%. Activation of alpha 2-adrenoceptors by oxymetazoline prevented the inhibitory effect of U 50,488, but not DAGO, on evoked [3H]DA release, whereas the selective kappa-antagonist nor-BNI antagonized the inhibition by oxymetazoline of [3H]DA, but not [3H]NA, release. In conclusion, activation of both kappa- and mu-opioid receptors results in an inhibition of evoked DA release from MBH slices but does not modulate NA release. Therefore, several of the reported effects of opioids on hormone secretion may be an (indirect) consequence of a reduction of DA release.(ABSTRACT TRUNCATED AT 250 WORDS)
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ABSTRACT: This study analyzes the impact of a neurotoxic lesion of the central noradrenergic system on the pharmacological reversal of the sexual inhibition present at sexual exhaustion, by IP treatment with yohimbine (2 mg/kg), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.25 mg/kg), and naloxone (3 mg/kg). All drugs, at the doses tested, were able to increase the percentage of sexually exhausted intact rats showing copulatory behavior 24 h after a sexual satiation session. In N-(2-chloroethyl)-N-ethyl-2-2-bromobenzylamine (DSP4)-lesioned, sexually exhausted animals, naloxone and 8-OH-DPAT lost their stimulatory effect on sexual behavior; yohimbine treatment was still able to markedly increase the percentage of satiated rats mounting, intromitting, and exhibiting the ejaculatory motor pattern, but inhibited seminal emission. The data strongly suggest that the integrity of the central noradrenergic system is essential for the pharmacological reestablishment of copulatory behavior in sexually exhausted rats. Results are in line with previous data showing that the sexual behavioral variables more directly addressing motivational components are severely affected by sexual satiation.Brain Research Bulletin 02/1995; 38(4):399-404. · 2.94 Impact Factor
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ABSTRACT: The antinociceptive effects of Delta9-tetrahydrocannabinol (Delta9-THC) have been widely described; however, its therapeutic potential may be limited by secondary effects. We investigated whether coadministration of low doses of cannabinoids or cannabinoids and morphine produced antinociception in the absence of side-effects. Effects of preadministration (i.p.) of Delta9-THC (1 or 2.5 mg/kg), cannabidiol (5 mg/kg), morphine (2 mg/kg), Delta9-THC + morphine, Delta9-THC + cannabidiol or vehicle on formalin-evoked nociceptive behaviour were studied over 60 min. Trunk blood and brains were collected 60 min after formalin injection and assayed for corticosterone and tissue levels of monoamines and metabolites, respectively. Drug effects on locomotor activity, core body temperature and grooming were assessed. Delta9-THC reduced both phases of formalin-evoked nociceptive behaviour, enhanced the formalin-evoked corticosterone response and increased the 4-hydroxy-3-methoxyphenylglycol : noradrenaline ratio in the hypothalamus. Cannabidiol alone had no effect on these indices and did not modulate the effects of Delta9-THC. Morphine reduced both phases of formalin-evoked nociceptive behaviour. Coadministration of Delta9-THC and morphine reduced the second phase of formalin-evoked nociceptive behaviour to a greater extent than either drug alone, and increased levels of thalamic 5-hydroxytryptamine. While the antinociceptive effects of Delta9-THC and morphine alone occurred at doses devoid of effects on locomotor activity, coadministration of Delta9-THC and morphine inhibited locomotor activity. In conclusion, coadministration of a low dose of morphine, but not cannabidiol, with Delta9-THC, increased antinociception and 5-hydroxytryptamine levels in the thalamus in a model of persistent nociception. Nevertheless, these enhanced antinociceptive effects were associated with increased secondary effects on locomotor activity.European Journal of Neuroscience 03/2004; 19(3):678-86. · 3.75 Impact Factor
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ABSTRACT: The role of dopamine receptors in the modulation of nucleus accumbens noradrenaline release was investigated in superfused rat brain slices. At concentrations of </=1 microM, dopamine enhanced, whereas at higher concentrations dopamine inhibited electrically evoked [3H]noradrenaline release. The D1 receptor agonist SKF-38393 increased, whereas the D2 agonist quinpirole inhibited evoked [3H]noradrenaline release. These effects were attenuated by the D1 antagonist SCH-23390 and the D2 antagonist (-)-sulpiride, respectively, indicating that accumbens noradrenaline release is regulated by stimulatory D1 and inhibitory D2 receptors. Whereas (-)-sulpiride enhanced, SCH-23390 did not reduce evoked accumbens [3H]noradrenaline release, indicating a tonic activation of D2 receptors only. Given the similar apparent affinity of dopamine for D1 and D2 receptors in striatal slices, the lack of tonic D1 receptor activation suggests that D1, unlike D2, receptors are extrasynaptically localized. No dopaminergic modulation of noradrenaline release was observed in rat medial prefrontal cortex or amygdala slices. To examine the regulation of accumbens noradrenaline release under conditions of increased dopaminergic activity, measurements were made using slices of amphetamine-pretreated rats. In these slices, the electrically evoked release of [3H]dopamine and [3H]noradrenaline was enhanced. The increasing effect of (-)-sulpiride on noradrenaline release was augmented, and SCH-23390 almost completely reversed this enhancement of [3H]noradrenaline release. These data suggest that whereas although under a moderate dopaminergic tone, accumbens noradrenaline release is mainly regulated by inhibitory D2 receptors, under circumstances of increased dopaminergic activity, recruitment of extrasynaptic stimulatory D1 receptors contributes to enhancement of noradrenaline release.Journal of Neuroscience 05/1999; 19(10):4123-31. · 6.91 Impact Factor