Abstract
In both humans and rats high levels of anxiety impair decision-making in the Iowa gambling task (IGT) in male subjects. Expression of the immediate early gene c-fos as marker of neural activity in rat studies indicated a role of the medial prefrontal cortex (prelimbic and infralimbic region; mPFC) in mediating the relationship between anxiety and decision-making. To delineate this relationship further and assess the underlying neurobiology in more detail, we inactivated in the present study the mPFC in male rats using a mixture of the GABA-receptor agonists muscimol and baclofen. Rats were exposed to the elevated plus maze (EPM) to measure effects on anxiety and to the rodent version of the IGT (r-IGT). Inactivation led to increased levels of anxiety on the EPM, while not affecting general activity. The effect in the r-IGT (trials 61–120) was dependent on levels of performance prior to inactivation (trial 41–60): inactivation of the mPFC hampered task performance in rats, which already showed a preference for the advantageous option, but not in rats which were still choosing in a random manner. These data suggest that the mPFC becomes more strongly involved as rats have learned task-contingencies, i.e., choose for the best long-term option. Furthermore they suggest, along with the data of our earlier study, that both anxiety and decision-making in rats are mediated through a neural circuitry including at least the mPFC. The data are discussed in relation to recent data of rodent studies on the neural circuitry underlying decision-making.
Highlights
We (De Visser et al, 2010) and others (Miu et al, 2008; conform Haegler et al, 2010) have shown that anxiety affects decision-making
Inactivation of the medial prefrontal cortex (mPFC) resulted in an increase in anxiety-related behavior without changes in general activity. r-Iowa gambling task (IGT) PERFORMANCE Good performing rats showed a lower fraction of visits to the disadvantageous arm than poor performing rats (0.52 ± 0.03; n = 12) at trial block 41–60
Various reasons may underlie these differences between studies including the present study, such as different procedures used, we show here that inactivation of the mPFC hampered task-progression for choosing the best long-term option in the rodent IGT (r-IGT) in good performing rats as predicted from our earlier study (De Visser et al, 2011)
Summary
We (De Visser et al, 2010) and others (Miu et al, 2008; conform Haegler et al, 2010) have shown that anxiety affects decision-making. The anterior cingulate cortex and dorso-lateral prefrontal cortex are involved in a negative feedback circuit of cortical control over limbic areas (Ridderinkhof et al, 2004; Bechara, 2005) The function of this top-down control circuit, that likely controls decision-making on the basis of reward and punishment as assessed in the IGT (Quirk et al, 2000; Miller and Cohen, 2001; Rogers et al, 2004; Davis et al, 2010; St Onge and Floresco, 2010), may be impaired in high anxious individuals (Bishop et al, 2004; Roiser et al, 2009), leading to suboptimal decision-making. The mPFC in rats has been suggested to share an anatomical and functional homology to the anterior cingulate cortex and dorso-lateral prefrontal cortex in humans (Uylings and van Eden, 1990; Brown and Bowman, 2002; Uylings et al, 2003)
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