Dissociation between mesocortical dopamine release and fear‐related behaviours in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions

Abstract

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.

Impulsivity Characterization in the Roman High- and Low-Avoidance Rat Strains: Behavioral and Neurochemical Differences

“…Moreover, the relationship between monoamine levels and impulsivity depends on the particular impulsive behavior evaluated (Winstanley et al, 2006, for review). Convergent evidence suggests that monoaminergic (at least DA and 5-HT) functional differences in the mesolimbic-mesocortical systems and related areas mediate the impulsivity-related behavioral traits that distinguish the Roman rat lines/ strains, including differential sensitivity to the effects of (and preference for) drugs of abuse (for reviews, see Charnay et al, 1995;Driscoll et al, 1980;Fattore et al, 2009;Fernández-Teruel et al, 2002a;Giorgi et al, 1994Giorgi et al, , 2003Giorgi et al, , 2007Guitart-Masip et al, 2006a, b, 2008aKulikov et al, 1995;Lecca et al, 2004). Collectively, the neurochemical findings reported in these studies suggest a relatively increased function (or tone) of DA and 5-HT neurotransmission in the RHA rat line/strain relative to RLA animals.…”

“…Abundant evidence implicates dopaminergic mechanisms in these differences. Compared with RLA rats, RHA rats show different dopaminergic responses: activation in the mesocortical dopaminergic pathway by stressors and anxiogenic drugs (Giorgi et al, 2003); more rapid baseline turnover rate of dopamine (DA) in the caudate nucleus (Driscoll et al, 1990); and more intense stereotypy in response to acute challenge with the DA receptor agonist apomorphine (Giménez-Llort et al, 2005).…”

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

“…Thus, it has been hypothesized that long-term exposure to drugs of abuse may alter the functional activity of dopaminergic afferent projections and glutamatergic neurons in frontocortical areas, with a consequent deficiency in the ability to inhibit inappropriate responses to drugs or drug-paired stimuli (Jentsch and Taylor, 1999;Everitt and Wolf, 2002;Chambers et al, 2003;Vanderschuren and Everitt, 2005). It is therefore noteworthy in this context that, compared with RLA rats, the mesocortical dopaminergic system of RHA rats is more robustly activated by both stressful and rewarding stimuli (D'Angio et al, 1988;Corda et al, 1997;Giorgi et al, 1999Giorgi et al, , 2003. In addition, RHA rats display higher scores than RLA rats in experimental paradigms used to assess sensation/ novelty seeking behavior in rodents (Siegel et al, 1993;Escorihuela et al, 1999;Fernández-Teruel et al, 2002;Steimer and Driscoll 2005).…”

“…Thus, compared with their RLA counterparts, RHA rats display a more robust sensation/novelty seeking profile, as well as higher baseline levels of impulsivity, and a marked preference for and intake of natural and drug rewards (Zeier et al, 1978;Siegel et al 1993;Escorihuela et al 1999;Giorgi et al 1999;Fernández-Teruel et al 2002). The phenotypic traits that distinguish these lines are at least partly determined by differences in the functional properties of their central dopaminergic pathways: (1) stressors and anxiogenic drugs activate the mesocortical dopaminergic projection of RHA, but not RLA, rats (D'Angio et al, 1988;Corda et al, 1997;Giorgi et al, 2003); (2) RHA rats have a higher density of D-1 dopamine (DA) receptors in the NAc (Giorgi et al, 1994); (3) the acute administration of psychostimulants and morphine causes a larger increment in motor activity and in DA output in the shell than in the core of the NAc of RHA, but not RLA, rats (Lecca et al, 2004); (4) the repeated administration of psychostimulants and morphine induces behavioral sensitization only in RHA rats Corda et al, 2005;Giorgi et al, 2005a); (5) in sensitized RHA rats, a subsequent challenge with these drugs elicits a more robust increment in DA output in the NAc-core, associated with an attenuated dopaminergic response in the NAc-shell, whereas these adaptive changes are not observed in sensitization-resistant RLA rats (Giorgi et al, 2005b(Giorgi et al, , 2007.…”

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

“…These findings suggest that RLA rats represent a valid genetic model to investigate the neural circuitry and molecular mechanisms underlying stress‐induced depression and, more specifically, to study depression associated with anxiety symptoms. Multidisciplinary studies aimed at identifying the central neuronal circuits involved in the above‐mentioned behavioral differences across the Roman lines have shown that their divergent phenotypic traits may be accounted for, at least in part, by differences in the functional responses of their central monoaminergic systems (D'Angiò, Serrano, Driscoll, & Scatton, 1988; Giorgi, Lecca, Piras, Driscoll, & Corda, 2003; Giorgi, Piras, Lecca, & Corda, 2005; Giorgi et al., 1994; Giorgi, Piras, et al., 2003 Giorgi et al., 2007, 2015; Lecca, Piras, Driscoll, Giorgi, & Corda, 2004; Sanna et al., 2015; Tournier et al., 2013). …”