Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats

Abstract

To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20–40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30–40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30–40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.

D2 Receptors and Sodium Ion Channel Blockades of the Basolateral Amygdala Attenuate Lithium Chloride-Induced Conditioned Taste Aversion Applying to Cancer Chemotherapy Nausea and Vomiting

“…Previous studies have suggested that the LiCl-induced conditioned suppression the saccharin solution intake was governed by the NAc, the anterior part of the bed nucleus of the stria terminals, and the central amygdala [ 15 ]. Moreover, the BLA and the prelimbic cortex were shown to exhibit more c-Fos expression after morphine- or amphetamine-induced conditioned suppression of the saccharin solution intake [ 36 , 37 , 38 , 39 ]. To date, no research has comprehensively examined the issue of whether the dopaminergic pathway or its subtypes of dopamine receptors from the BLA projections to the other brain areas, such as the NAc, VTA, or the subareas of the medial prefrontal cortex (i.e., the cingulate area 1, prelimbic cortex, and infralimbic cortex), actually contribute to the LiCl-induced CTA learning.…”

“…On the other hand, the present study used the emetic drug, LiCl, to induce conditioned suppression of saccharin solution intake. However, another line of behavioral studies has demonstrated that abused drugs (such as morphine [ 38 ], cocaine [ 40 ], amphetamines [ 41 ], and alcohol [ 42 ]) could also have the effect of conditioned suppression on the tastant. Until now, no research has examined whether the pathway and dopaminergic receptors of the BLA also mediate abused drug-induced conditioned suppression.…”