A23187, free acid The lactam compounds including ceftriaxone

The β-lactam compounds, including ceftriaxone (CEF), have shown to attenuate drug-seeking in several drugs of abuse including methamphetamine [31], cocaine [32,33], nicotine [34] and morphine [35]. Moreover, in our laboratory, we have shown that CEF can reduce chronic alcohol drinking via upregulating both the expressions of GLT-1 and xCT in P rats [36,37]. Therefore, we hypothesized here that the administration of CEF during the extinction phase would attenuate HYD reinstatement by modulating these transporters. Thus, several important A23187, free acid rewards regions involved in the glutamatergic transmission were investigated such as the dorsomedial prefrontal cortex (dmPFC), NAc, HIP and amygdala (AMY).
Materials and methods
Results
Discussion The CPP paradigm has been used to measure opioid rewards, including heroin [53,54], morphine [55,56], HYD [38] and other drugs of abuse. In this study, the CPP paradigm was adopted from previous work in our laboratory on cocaine reinstatement [33]. Several studies have focused on the association between the glutamatergic system and the reinstatement of morphine and heroin [10,11]. However, to the best of our knowledge, the association between HYD reinstatement and the glutamatergic system has not been thoroughly investigated, especially in P rats. In this study, we used HYD (5 mg/kg, i.p.) to produce the preference and reinstatement in P rats. Importantly, we found that HYD reinstatement was associated with downregulation of xCT in the NAc and HIP and these effects were attenuated with CEF treatment. This study investigated the NAc (both core and shell), since this brain region is involved in opioid rewards [57], withdrawal [58] and tolerance [59]. It has been found that blocking the mu-opioid receptor in the NAc diminished heroin rewards in rats [57]. Moreover, high extracellular concentration of glutamate in the NAc core has been linked to heroin-seeking behavior and relapse [11]. Also, it has been shown that injecting mGluR2/3 agonist (LY379268) into the NAc shell, but not NAc core, attenuated heroin-seeking behavior [60]. Both NAc core and shell receive projections from the dmPFC [for review, see [61]. It is important to note that glutamatergic projections from the PFC to NAc are suggested to be involved in cocaine- and heroin-seeking behavior [11,62]. In this study, we also focused on the dmPFC, which included the cingulate cortex and prelimbic cortex. The activation of the cortex area in drug addiction was shown in neuroimaging studies during intoxication and craving, but not in withdrawal [for review see Ref. [63]. The mPFC appears to be involved in the acquisition of morphine, but not the reinstatement [64]. It has been suggested that there is a link between the PFC and cue-induced heroin-seeking [65]. The cingulate cortex was reported to be activated following exposure to psychostimulant drugs such as cocaine [66,67]. In addition, it was reported that the cingulate cortex neural activity was altered in heroin users using the functional magnetic resonance imaging [68]. The inactivation of the prelimbic cortex was shown to block the reinstatement of heroin [11,69] and methamphetamine [70]. Moreover, others have shown that activating the prelimbic cortex could facilitate heroin reinstatement [71]. Moreover, the projections from the VTA to the NAc were suggested to be more important in opioid reinstatement as compared to the PFC [72], which might explain why this latter brain region was not affected in HYD reinstatement. The HIP was investigated which included (CA1, CA2 and CA3). This brain region is involved in learning and memory function [73]. Studies have reported that HIP is implicated in the association between the environmental context and unconditioned stimuli (foot-shock) [74, 75]. A number of studies have demonstrated that the HIP is crucial for drug-seeking behavior [[76], [77], [78]]. This brain region is believed to be associated with negative contextual experience associated with withdrawal from several drugs of abuse [for review, see ref [79]. It has also been found that heroin can increase the amount of polysialic acid-neural cell adhesion molecule expression in glial cells, which could explain the damage found in the HIP area in postmortem heroin addicts [80]. On the other hand, we investigated the AMY which included (central amygdala, basomedial amygdala and basolateral amygdala). It has been suggested that the AMY facilitates the drug reward, learning and seeking behaviors in rats [81]. In addition, lesions in the AMY were shown to prevent cocaine reinstatement [82]. Also, It has been found that inactivation of AMY using tetrodotoxin, potent neurotoxin, blocked the heroin-seeking behavior in rats [83].