Tolerance to repeated rewarding electrical stimulation of the parabrachial complex

Differential rewarding effects of electrical stimulation of the lateral hypothalamus and parabrachial complex: Functional characterization and the relevance of opioid systems and dopamine

“…This result may be related to the important role for addicted individuals of the places in which the drugs are taken (Koob and Le Moal, 2000; Koob et al, 2014) and to the development of dependency and/or tolerance with repeated administrations (See, 2002). In this regard, a tolerance effect has been observed after repeated stimulation of the LPBe, especially when administered passively (not contingently) by the experimenter (Hurtado and Puerto, 2016, 2018) These findings are in agreement with the report by other authors that withdrawal reactions were precipitated by a peripherally acting opioid antagonist that generated activation throughout the visceral pathway, specifically in the LPBe (Hamlin et al, 2001).…”

“…This conceptual framework, subsequently developed by Koob and Le Moal, focuses on motivational-affective circuits/systems and hypothesizes that transition towards compulsive use and loss of control is accompanied by chronic perturbations of homeostatic systems (allostasis) and by neuroadaptations, leading to behavioural sensitization (Koob and Le Moal, 2000; Koob et al, 2014). Accordingly, the presence in the brainstem of regions such as the LPBe, which process opiate-mediated positive (and/or aversive) affective information (Garcia et al, 2014; Simon et al, 2007, 2008, 2009, 2011, 2013) and where a tolerance effect has been observed (Hurtado and Puerto, 2016; Hurtado et al, 2016), suggests that this region may possibly form part of wider hedonic-affective circuits that may be hierarchically controlled by anterior prosencephalic regions (Berridge and Kringelbach, 2015; Roitman et al, 2004) and whose components require further elucidation.…”