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

1 The pharmacological modulation of opioid actions by drugs acting on heter ologous mechanisms could be useful to overcome some of the main problems as sociated with the use of opiate agonists. Based on previous findings on the interactions between yohimbine and opioid drugs, we have further studied t he effects of yohimbine on the antinociceptive and positive-negative reinfo rcing effects of morphine (mu opioid receptor-preferring agonist), U-50,488 (kappa agonist) and SNC80 (delta agonist). 2 Pretreatment with yohimbine completely blocked the antinociception provid ed by the three opioid agonists in the mouse tail-immersion test. 3 A similar blockade of SNC80 and U-50,488-induced antinociception was obse rved with yohimbine in the mouse hot plate test at the same doses. In this paradigm, the effect of the kappa agonist was very slight and the actions o f yohimbine rather variable. 4 In place conditioning experiments with SD (Sprague-Dawley) male rats, yoh imbine alone was inactive but it limited the preference induced by morphine and SNC80 and the aversive effect 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 mu and delta opioid agonists. More selective dru gs could help to understand the mechanisms involved in these actions.