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Response-noncontingent cocaine administration is particularly prone, compared to response-contingent administration, to induce behavioral and biochemical sensitization.

Response-contingent nicotine SA preferentially increases the DA output in the NAc shell as compared to that in the core, independently from the duration of the nicotine exposure. Increase in NAc DA is strictly related to nicotine action since is not observed during extinction in spite of active responding.

The mesocortical and mesolimbic dopaminergic (DAergic) pathways are activated by either aversive or rewarding stimuli. The functional tone of these DAergic neurons also increases during the execution of cognitive tasks. The present study was designed to examine the relationship between mesocortical and mesolimbic DAergic function and the expression of fear-related behaviours as compared with attention- and cognition-related mechanisms (e.g. coping strategies), in response to aversive conditions. To this aim, we used two psychogenetically selected rat lines, Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh), which display drastically different emotion- and coping-related behaviours in response to stressors: RLA/Verh rats are 'reactive copers' and more fearful than RHA/Verh rats, which are 'proactive copers'. Brain dialysis experiments demonstrated that tail-pinch (TP) and the anxiogenic compounds pentylenetetrazol (PTZ) and ZK 93426 increased DA output in the medial prefrontal cortex (PFCX) of RHA/Verh but not RLA/Verh, rats. In contrast, in the shell compartment of the nucleus accumbens (NAC shell), TP caused a small increase in DA output only in RLA/Verh rats, whereas PTZ and ZK 93426 had no significant effect on either line. RHA/Verh rats displayed more robust and longer lasting coping activity and less frequent freezing and self-grooming episodes than did RLA/Verh rats after TP, PTZ or ZK 93426. This dissociation between fear-related behaviour and cortical DAergic activation argues against the view that the latter may be involved in the control of fear-like responses. We therefore propose that the activation of mesocortical DAergic projections by aversive stimuli underlies the cognitive mechanisms that are triggered in an attempt to gain control over the stressor.

Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding.

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