Systemic idazoxan impairs performance in a non-reversal shift test: implications for the role of the central noradrenergic systems in selective attention

Abstract

Two experiments examined the effect of pharmacological stimulation of the locus coeruleus in a non-reversal shift paradigm to test predictions concerning the role of the ceruleo-cortical noradrenergic system in processes of selective attention. Food-deprived rats were trained to make either visual (experiment 1) or spatial (experiment 2) discriminations in a parallel alley with both sets of cues being present at all times. Two groups of rats received treatments of either 2 mg/kg i.p. of the selective α(2) adrenoceptor antagonist idazoxan or saline control injections before each daily block of trials. Following attainment of criterion, the reinforcement contingencies were altered according to a non-reversal shift design, so that the alternative (i.e. either spatial or visual) set of cues now predicted reward. Rats treated with idazoxan were not impaired in the acquisition of either the spatial or visual discrimination task, but they were impaired in both forms of non-reversal shift. These deficits are interpreted as resulting from narrowed attention in idazoxan-treated rats, thus supporting a selective attention hypothesis of locus coeruleus function.

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour

“…Thus, although presynaptic modulation of NA function with the low doses of clonidine used in the current study had little effect on the efficiency of attentional shifting compared to spatial memory (Coull et al 1995a), more profound disruption of the NA system through the additional effects of an α 2 antagonist reveals that NA does have a role in the redirection of an attentional set towards newly relevant environmental stimuli. Such evidence is consistent with reports of narrowed attentional focus in rats during the acquisition of non-reversal shifts following administration of idazoxan (Rowe et al 1996).…”

Cognitive Flexibility in the Context of Stress and Depressive Disorders

“…Moreover, the levels of NE that are released during alert, non-stressed periods optimize prefrontal cognitive functioning by engaging α2A-receptors (Arnsten & Goldman-Rakic, 1985), whereas the high levels of NE that are released in response to a stressor impair PFC-related cognitive processes by stimulating lower-affinity α1-receptors and β1-receptors (Birnbaum et al, 1999;Ramos et al, 2005). In line with these findings, blockade of α1 receptors in rats improved set-shifting, whereas chronic α2 receptor antagonism had the opposite effect (Rowe et al, 1996). Likewise, it has been reported that intra-medial PFC infusions of a postsynaptic α1 receptor antagonist prevented the attentional set-shifting improvement observed following systemic injections of an adrenergic auto-receptor antagonist (atipamezole) in rats (Lapiz and Morilak, 2006).…”

Lesions of the dorsal noradrenergic bundle impair attentional set‐shifting in the rat

“…Other early studies of effects of DNAB lesions on ED‐shifting in rats in a paradigm utilizing shifts between spatial and visual cues were confounded by deficits in acquisition (Mason & Lin, 1980). The effects of systemic manipulations of drugs such as the NA adrenoceptor‐2 antagonist idazoxan on similar spatial to visual shifts (Devauges & Sara, 1990) were not confirmed when a fully counterbalanced design was employed (Rowe et al ., 1996). However, recent findings of a role for postsynaptic α‐2 receptors in the mPFC in the ED‐shift are fully consistent with the findings of the present study (Lapiz & Morilak, 2006).…”