Abstract
There are several experimental studies which suggest opioids consumption forms pathological memories in different brain regions. For example it has been empirically demonstrated that the theta rhythm which appears during chronic opioid consumption is correlated with the addiction memory formation. In this paper, we present a minimal computational model that shows how opioids can change firing patterns of the neurons during acute and chronic opioid consumption and also during withdrawal periods. The model consists of a pre- and post-synaptic neuronal circuits and the astrocyte that monitors the synapses. The output circuitry consists of inhibitory interneurons and excitatory pyramidal neurons. Our simulation results demonstrate that acute opioid consumption induces synchronous patterns in the beta frequency range, while, chronic opioid consumption provokes theta frequency oscillations. This allows us to infer that the theta rhythm appeared during chronic treatment can be an indication of brain engagement in opioid-induced memory formation. Our results also suggest that changing the inputs of the interneurons and the inhibitory neuronal network is not an appropriate method for preventing the formation of pathological memory. However, the same results suggest that prevention of pathological memory formation is possible by manipulating the input of the stimulatory network and the excitatory connections in the neuronal network. They also show that during withdrawal periods, firing rate is reduced and random fluctuations are generated in the modeled neural network. The random fluctuations disappear and synchronized patterns emerge when the activities of the astrocytic transporters are decreased. These results suggest that formation of the synchronized activities can be correlated with the relapse. Our model also predicts that reduction in gliotransmitter release can eliminate the synchrony and thereby it can reduce the likelihood of the relapse occurrence.
Highlights
Addiction is believed to be a pathological memory which is formed in different brain regions, especially in the Ventral Tegmental Area (VTA), Nucleus Accumbens (NA), Prefrontal Cortex (PC), and the hippocampus (Berke and Hyman, 2000; Boening, 2001; Nestler, 2001, 2013; Kauer and Malenka, 2007; Kalivas and O’Brien, 2008; Dong and Nestler, 2014)
The bottom panel describes the spectrogram of the population spike count (PSC)
Since based on experimental observations induction of the theta frequency is linked to the memory formation process, probably our results suggest that the neurons learn the memory of addiction process
Summary
Addiction is believed to be a pathological memory which is formed in different brain regions, especially in the Ventral Tegmental Area (VTA), Nucleus Accumbens (NA), Prefrontal Cortex (PC), and the hippocampus (Berke and Hyman, 2000; Boening, 2001; Nestler, 2001, 2013; Kauer and Malenka, 2007; Kalivas and O’Brien, 2008; Dong and Nestler, 2014). It has been shown that activation of the opioid receptors can decrease the release of the GABA with a disinhibitory mechanism, and as a result glutamatergic transmissions increase (Caudle and Chavkin, 1990; Chen and Marine, 1991; Capogna et al, 1993; Kow et al, 2002; McQuiston and Saggau, 2003; Blaesse et al, 2015). These modifications can contribute to memory formation process (Borjkhani et al, 2018). Many researchers suggested that the astrocytes play fundamental roles in the formation of addiction (López-Hidalgo et al, 2012; Borjkhani et al, 2014, 2018; Scofield and Kalivas, 2014; Harada et al, 2015; Wang et al, 2017)
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