The present study tested whether rewarding and/or aversive neural substrates involved in morphine-induced conditioned taste suppression during conditioning, extinction, and reinstatement to examine the reward comparison hypothesis and the paradoxical effect hypothesis of abused drugs. We induced conditioned suppression using both a 0.1% saccharin solution and injected morphine and compared the results in the conditioning, extinction, and reinstatement phases. Both c-Fos and phosphorylation extracellular signal-regulated kinase (p-ERK) were labeled during the three phases to show the immunohistochemical activity in rewarding and/or aversive neural substrates. The data of c-Fos or p-ERK labeling showed that the rewarding nucleus accumbens and dentate gyrus, the aversive prelimbic cortex and inflralimbic cortex, and the rewarding and aversive basolateral cortex involved in conditioning. The rewarding nucleus accumbens and piriform cortex, the aversive prelimbic cortex and inflralimbic cortex, and the rewarding and aversive lateral hypothalamus involved in extinction. The rewarding nucleus accumbens and piriform cortex, the aversive cingulated cortex area 1, prelimbic cortex, inflralimbic cortex, and central amygdala, and the rewarding and aversive basolateral amygdala and lateral hypothalamus involved in reinstatement. The hyperactivity of the brain is distributed in many places due to disturbance and non-homeostasis in the brain. For the stress and aversive index, the corticosterone level of the morphine group was hyperactive during conditioning and reinstatement but not during extinction or at baseline. The results challenge the reward comparison hypothesis and directly support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in clinical treatment of drug addiction.
Keywords: morphine, reward comparison hypothesis, the paradoxical effect hypothesis of abused drugs, c-Fos, p-ERK, rat.