Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat

Abstract

Addictive drugs have been shown to severely influence many neuronal functions, which are considered as the underlying mechanisms for physiological and psychological dependences. We previously showed that in vivo LTP in rat hippocampal CA1 region is significantly reduced during withdrawal following chronic opiates treatment, and the reduced LTP can be restored by re-exposure of animals to corresponding drugs. Here, we further demonstrated that during opiates withdrawal, the re-exposure of morphine either systemically (subcutaneously) or locally (intracerebroventricularly) could restore the reduced LTP in heroin-dependent rats, but heroin could not restore the reduced LTP, in morphine-dependent rats, indicating differential modulations of hippocampal functions by those two opiates. In contrast, DAMGO, a mu-opioid receptor (MOR) agonist, could restore the reduced LTP, and CTOP, a MOR antagonist, could block the restoration in rats dependent on both opiates, showing that MOR is functional under such conditions. However, the upregulation of hippocampal PKA activity during morphine withdrawal could be suppressed by re-exposure of morphine but not that of heroin, suggesting a likely underlying mechanism of the differential modulation of LTP by two opiates. Taken together, our study clearly demonstrates that chronic abuse of opiates inevitably leads to severe alteration of hippocampal LTP, and reveals the interesting differences between morphine and heroin in their effects on the differential modulation of hippocampal synaptic plasticity.

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

“…It is worth noting, however, that reductions in NAc core A/N ratios due to up-regulation of NR2B-containing NMDAR currents have been reported following heroin self-administration in rats, and that this adaptation drives reinstatement of heroin seeking (24). The mechanisms underlying this apparent discrepancy in plasticity are unclear; however, morphine and heroin have been shown to differentially modulate synaptic strength (44). Furthermore, distinctions in learning and motivational processes associated with operant responding tasks vs. CPP, as well as incorporation of extinction vs. abstinence following drug exposure may be contributing factors to these differences.…”

Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A1Receptors

“…In addition, previous studies have shown that hippocampal LTP is reduced by chronic morphine treatment (Pu et al, 2002;Bao et al, 2007). Based on these findings, we therefore determined whether the extracellular adenosine accumulation could contribute to the impairment of LTP by activation of adenosine A 1 receptors in response to chronic morphine treatment.…”

“…Accumulating evidence demonstrates that it also plays a role in opioid dependence (Done et al, 1992;Fan et al, 1999;Lu et al, 2000;Rezayof et al, 2003). Several studies have shown that chronic exposure to morphine or heroin leads to the impairment of hippocampal LTP (Pu et al, 2002;Salmanzadeh et al, 2003;Bao et al, 2007) and induces cognitive deficits, as shown by poor performances on memory task of heroin abusers (Guerra et al, 1987) or chronic opiatetreated rodents (Spain and Newsom, 1991;Li et al, 2001;Pu et al, 2002;Miladi Gorji et al, 2008). However, the mechanisms underlying these effects of opiates are poorly understood.…”

An intriguing association between dental and mental pathology in addicted and control subjects: a cross-sectional survey

“…57 Similarly, it is now well known that there is intense interest in the role of stem cells in the adult brain, particularly with reference to function in memory [69][70][71] and emotional stability, [72][73][74][75] two areas which are particularly vulnerable in drug addiction. [76][77][78] A focus on cellular health, growth renewal and replication as is suggested in general terms by this report explains several seeming paradoxes in addiction medicine, such as a fi nding that on a genome-wide screen for genes up-regulated in addiction, genes corresponding to synapse formation, intracellular signalling and transcription factors were found to be most signifi cantly altered 79 and have been specifi cally identifi ed in studies of brain ageing. 80 Cortical regions such as the prefrontal lobes, the right inferior frontal gyrus, the dorsolateral prefrontal cortex, the anterior cingulate and the deep white matter of the frontal lobes, well known to be impaired in addiction, 54,55 have also been identifi ed as sites particularly vulnerable to age-related declines.…”