2 Matching Annotations
  1. Jun 2016
  2. Jan 2016
    1. The regional brain activation responses to a stimulant drug also differ between controls and cocaine abusers in ventral prefrontal regions. In control subjects, intravenous stimulant administration decreased the activity of ventral medial frontal regions (OFC and ventral ACC), whereas in cocaine abusers, it activated these regions, which are involved in salience attribution and conditioning (Dosenbach et al., 2006, O’Doherty et al., 2001 and Shackman et al., 2011). Activation of the OFC in cocaine abusers was associated with craving (Volkow et al., 2005). In contrast, activity in the right inferior frontal region Ba 44, a key brain region involved in inhibitory control (Aron et al., 2004), was associated with the deactivation of the NAc and ventral PFC upon successful control of cocaine craving (Volkow et al., 2010). This pattern of responses uncovers distinct contributions of PFC regions to addiction on the basis of their striatal projections: dlPFC and inferior frontal regions that project to the dorsal caudate facilitate self-control, whereas ventral PFC regions projecting to NAc facilitate drug taking (Goldstein and Volkow, 2011). This is also consistent with preclinical findings that identified distinct contributions of prelimbic mPFC (PL) and infralimbic mPFC (IL) to cocaine seeking in rats (review in Bossert et al., 2013). Studies using the reinstatement model of relapse found that, after extinction of cocaine self-administration, PL activity promoted cocaine seeking while IL activity inhibited it (Peters et al., 2008). Importantly, in the incubation of the cocaine-craving model (response to cocaine cues progressively increases with time after withdrawal), reversible inactivation of IL, but not PL, decreased “incubated” cue-induced cocaine seeking after prolonged withdrawal, while pharmacological activation of IL, but not PL, increased cocaine seeking during early withdrawal (Koya et al., 2009). However, in the same animal model, optogenetic inhibition of PL neurons (projecting to NAc core) that previously underwent a specific form of cocaine-induced synaptic plasticity (recruitment of silent synapse) decreased incubation of craving, while the opposite effect was observed following inhibition of the IL projection to NAc shell (Di Forti et al., 2014). In clear contrast, in a punishment-induced suppression model of “compulsive” cocaine seeking, in which most rats suppressed cocaine self-administration by shock punishment while a few did not (punishment-resistant “compulsive” rats), optogenetic stimulation of PL inhibited cocaine seeking in punishment-resistant rats while optogenetic inhibition increased it (Chen et al., 2013). However, in the same model, excitotoxic lesions of the PL or IL had no detectable effect on cocaine seeking in punishment-resistant rats (Pelloux et al., 2013). Taken together, the PL and IL appear to play different and complex roles in cocaine-seeking behaviors in rat addiction models, which are highly dependent on the particular behavior being assessed and the experimental procedure used to manipulate local neuronal activity. The results underscore the complexity of the neuroplasticity within the mPFC circuitry, a multimodal brain structure involved in the orchestration of diverse behaviors.