The role of mu1 opioid receptors in the stimulation of dopamine transmission in the rat nucleus accumbens by an unusual palatable food (Fonzies) and non-psychostimulant drugs of abuse was investigated by the use of naloxonazine, a pseudo-irreversible antagonist of mu1 opioid receptors. Feeding of Fonzies stimulated dopamine release in the medial prefrontal cortex and in the shell, but not in the core of the nucleus accumbens. Pretreatment with naloxonazine given systemically (15 mg/kg i.p. 20 h before) completely prevented the stimulation of dopamine release in the shell of the nucleus accumbens by Fonzies without affecting that in the prefrontal cortex. Systemic pretreatment with naloxonazine reduced or, depending on the dose, abolished, the stimulation of dopamine release in the nucleus accumbens shell by morphine, nicotine and ethanol, but did not affect that by haloperidol. Naloxonazine also prevented the stimulatory effects of Fonzies, nicotine and morphine on nucleus accumbens dopamine transmission when infused bilaterally in the ventral tegmental area. The results indicate that mu1 opioid receptors in the ventral tegmentum play a major role in the stimulant effects of food and drugs of abuse on mesolimbic dopamine transmission.