Abstract
The addictive properties of opioids may be mediated to some extent by cocaine-and amphetamine-regulated transcript (CART) in the reward pathway. Moreover, some claims CART interacts with the glutamate system. Here, we evaluated whether intra-nucleus accumbens (NAc) shell infusions of CART induces Conditioned Place Preference (CPP) or Conditioned Place Aversion (CPA) and affects morphine reward. We also measured NR1 subunit expressions of the N-methyl-d-aspartate (NMDA) receptor in various parts of the reward pathway (NAc, prefrontal cortex and hippocampus) after conditioning tests. Animals with bilateral intra-NAc shell cannulas were place-conditioned with several doses of subcutaneous morphine prior to intra-NAc shell infusions of artificial cerebrospinal fluid (aCSF). Immunohistochemistry (IHC) showed a dose-dependent increase in the NR1 expression in all examined parts. When rats were conditioned with intra-NAc shell infusions of CART, CPP and CPA induced with 2.5 and 5 μg/side respectively and IHC showed NR1elevation with 2.5 and reduction with 5 μg/side in all areas. Sub-rewarding dose of CART administration (1.25 μg/side) prior to sub-rewarding dose of morphine (2.5 mg/kg) induced CPP and NR1 increased in all examined tissues in IHC. However, infusion of an aversive dose of CART (5 μg/side) prior to the rewarding dose of morphine (5 mg/kg) produced neither CPP nor CPA and NR1 in the NAc and hippocampus decreased significantly. It seems that the rewarding or aversive effects of intra-NAc shell CART and its facilitating or inhibiting effects on morphine reward are dose-dependent. Additionally, NMDA may be closely involved in the affective properties of opioids and CART in the reward pathway.
Highlights
Infusion of an aversive dose of cocaine- and amphetamineregulated transcript (CART) (5 μg/side) prior to the injection of a rewarding dose of morphine (5 mg/kg) produced neither conditioned place preference (CPP) nor conditioned place aversion (CPA) and IHC data showed a significant decrease in the amount of NR1 subunit in the nucleus accumbens (NAc) and hippocampus
The NMDA receptor may be closely involved in the affective properties of opioids and CART in the reward pathway
Further studies are needed in this regard to evaluate the effect of CART peptide administration on NR1 subunit expression in NMDA receptor. This is the first study aimed at evaluation of the possible interaction between CART 55–102, opioid and NMDA glutamate system in the framework of the NAc
Summary
Nucleus Accumbens (NAc) as a part of the pathway is a significant target of addictive drugs [2] and has different neurotransmitter systems which modulate the reinstatement of drugseeking behavior [3]. The role of glutamate in the neuroplasticity of the reward pathway, especially the circuitry from the prefrontal cortex (PFC) to the NAc is undeniable [6]. We have evaluated whether intra-nucleus accumbens (NAc) shell infusions of CART induces CPP or CPA and affect morphine reward. We have measured the expression of the NR1 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor in various parts of the reward pathway (NAc, prefrontal cortex (PFC), and hippocampus) after conditioning tests. Rats were conditioned with intra-NAc shell infusion of different doses of CART. CPP and CPA were induced with 2.5 and 5 μg/side, respectively
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