Subthalamic low-frequency oscillations predict vulnerability to cocaine addiction

Abstract

Identifying vulnerable individuals before they transition to a compulsive pattern of drug seeking and taking is a key challenge in addiction to develop efficient prevention strategies. Oscillatory activity within the subthalamic nucleus (STN) has been associated with compulsive-related disorders. To study compulsive cocaine-seeking behavior, a core component of drug addiction, we have used a rat model in which cocaine seeking despite a foot-shock contingency only emerges in some vulnerable individuals having escalated their cocaine intake. We show that abnormal oscillatory activity within the alpha/theta and low-beta bands during the escalation of cocaine intake phase predicts the subsequent emergence of compulsive-like seeking behavior. In fact, mimicking STN pathological activity in noncompulsive rats during cocaine escalation turns them into compulsive ones. We also find that 30 Hz, but not 130 Hz, STN deep brain stimulation (DBS) reduces pathological cocaine seeking in compulsive individuals. Our results identify an early electrical signature of future compulsive-like cocaine-seeking behavior and further advocates the use of frequency-dependent STN DBS for the treatment of addiction.

A self-adjusting, progressive shock strength procedure to investigate resistance to punishment: Characterization in male and female rats

“…It is possible that motivation in progressive ratio schedules is mostly dependent on reward neurotransmitters such as dopamine (Cagniard et al, 2006;Ko and Wanat, 21 2016;Kravitz et al, 2012;Randall et al, 2012), endoopioids and endocannabinoids (Solinas and Goldberg, 2005) whereas resistance to punishment depends also on brain serotonin levels (Cohen et al, 2015;Pelloux et al, 2012); it is also possible that the balance between these two systems (Palminteri and Pessiglione, 2017) and/or the involvement of other neurotransmitters such as glutamate and GABA (Stephenson-Jones et al, 2020) participate in determining individual differences. Importantly, consistent with previous studies (Degoulet et al, 2021;Li et al, 2021), sensitivity to aversion does not seem to be responsible for differences in punishment because pain sensitivity in the hot-plate test did not differ between resistant and sensitive rats. Future studies are needed to investigate the precise mechanisms responsible for resistance to punishment in the PSS procedure.…”

A self-adjusting, progressive shock strength procedure to investigate resistance to punishment: characterization in male and female rats

“…It is possible that motivation in progressive ratio schedules is mostly dependent on reward neurotransmitters such as dopamine (Cagniard et al, 2006; Ko and Wanat, 2016; Kravitz et al, 2012; Randall et al, 2012), endoopioids and endocannabinoids (Solinas and Goldberg, 2005) whereas resistance to punishment depends also on brain serotonin levels (Cohen et al, 2015; Pelloux et al, 2012); it is also possible that the balance between these two systems (Palminteri and Pessiglione, 2017) and/or the involvement of other neurotransmitters such as glutamate and GABA (Stephenson-Jones et al, 2020) participate in determining individual differences. Importantly, consistent with previous studies (Degoulet et al, 2021; Li et al, 2021), sensitivity to aversion does not seem to be responsible for differences in punishment because pain sensitivity in the hot-plate test did not differ between resistant and sensitive rats. Future studies are needed to investigate the precise mechanisms responsible for resistance to punishment in the PSS procedure.…”

Behavioral and Brain Reactivity Associated With Drug-Related and Non-Drug-Related Emotional Stimuli in Methamphetamine Addicts

“…Addicts often exhibit both impulsive and compulsive behaviors. In particular, they engage in compulsive drug taking despite the desire to stop taking the drug (Degoulet et al, 2021). Even after long periods of withdrawal treatment, once re-exposed to the drug environment, addicts are prone to relapse (Bechard and Knackstedt, 2019).…”