Effects of yohimbine on the antinociceptive and place conditioning effects of opioid agonists in rodents

Abstract

1 The pharmacological modulation of opioid actions by drugs acting on heterologous mechanisms could be useful to overcome some of the main problems associated with the use of opiate agonists. Based on previous ®ndings on the interactions between yohimbine and opioid drugs, we have further studied the e ects of yohimbine on the antinociceptive and positive-negative reinforcing e ects of morphine (m opioid receptor-preferring agonist), U-50,488 (k agonist) and SNC80 (d agonist). 2 Pretreatment with yohimbine completely blocked the antinociception provided by the three opioid agonists in the mouse tail-immersion test. 3 A similar blockade of SNC80 and U-50,488-induced antinociception was observed with yohimbine in the mouse hot plate test at the same doses. In this paradigm, the e ect of the k agonist was very slight and the actions of yohimbine rather variable. 4 In place conditioning experiments with SD (Sprague ± Dawley) male rats, yohimbine alone was inactive but it limited the preference induced by morphine and SNC80 and the aversive e ect of U-50,488. Impaired novelty preference was also observed with the combination of yohimbine and U-50,488. 5 It is concluded that yohimbine tends to limit opioid antinociception and the addictive potential of m and d opioid agonists. More selective drugs could help to understand the mechanisms involved in these actions.

Effects of RGH-237 [N-{4-[4-(3-Aminocarbonyl-phenyl)-piperazin-1-yl]-butyl}-4-bromo-benzamide], an Orally Active, Selective Dopamine D3Receptor Partial Agonist in Animal Models of Cocaine Abuse

“…BP-897 has still considerable affinity to 5-HT 1A and ␣ 2 receptors, being partial agonist on the former and antagonist on the latter receptor (Cussac et al, 2000). However, 5-HT 1A agonists and partial agonists caused place preference (Tzschenke, 1998), whereas there are conflicting data with ␣ 2 antagonists; idazoxan induced place preference, whereas yohimbine was shown to produce place aversion or no effect (Tzschenke, 1998;Morales et al, 2001;Sahraei et al, 2004). Finally, even the D 2 antagonist character of BP-897 does not give a clue because the highly potent D 2 antagonist haloperidol reproducibly showed inefficacy in place conditioning (Tzschenke, 1998).…”

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

“…Yohimbine, a selective a 2 adrenoceptor antagonist (Goldberg and Robertsson, 1983) with very low affinity for I 1 binding sites (I 1 /a 2 affinity ratio ¼ 0.01; Ernsberger et al, 1987Ernsberger et al, , 1992Hamilton et al, 1988;Senard et al, 1990), with a dose of 0.005 mg/kg is incapable of affecting place preference or altering morphine CPP; however, it completely blocks the potentiating effect of agmatine on morphineinduced place preference. Yohimbine with higher doses is shown to induce CPA (File, 1986) and it tends to limit the place preference induced by morphine (Morales et al, 2001). This discrepancy would be explained by administration of lower doses of yohimbine in the present work.…”

“…Clonidine blocks the rewarding effects of morphine in rats withdrawn from morphine; however, it has no effect on morphine-induced CPP in drug naïve animals (Nader and Van der Kooy, 1996). Yohimbine is shown to limit the preference induced by morphine in male rats (Morales et al, 2001). …”

Antinociceptive Effect of the Endemic Species Nepeta depauperata Benth

“…In the hot plate test which consists of a thermal stimulus, an increase in the reaction time is generally considered as an important parameter for evaluating central antinociceptive activity (6,7). Relative to controls, the studied extract increased significantly the mice hot plat reaction time.…”