The monoaminergic and cholinergic systems are implicated in different forms of behavioral arousal that can be dissected in terms of their forebrain targets and the nature of the behavioral processes they modulate in distinct regions. Thus, evidence in rats with selective neurochemical manipulations tested behaviorally using an analog of an attentional task developed for human subjects indicates that the coeruleo-cortical noradrenergic system is implicated in divided and selective attention, the basal forebrain cholinergic system in stimulus detection, the mesostriatal and mesolimbic dopaminergic systems in response speed and vigor, and the mesencephalic serotoninergic or 5-HT systems in response inhibition. Our recent studies have focused on fractionating, in the same task, the differential contributions of the dorsal and median raphé 5-HT systems as well as elucidating the functions of the mesocortical dopaminergic system, each of which may be relevant to understanding the behavioral and cognitive sequelae of cocaine administration in human subjects as well as in experimental animals.

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.

No abstract

No abstract

Durantou, F., P. Cazala, and B. Pourrias: Evidence for an action of heptaminol hydrochloride (Hept-a-mylR) on the central nervous system based on an increase in intracranial self-stimulation behavior in the mouse. Drug Dev. Res. 20:465-472, 1990.The effects of intraperitoneal injections of heptaminol hydrochloride (Hept-a-mylR) on intracranial self-stimulation (ICSS) in the lateral hypothalamus (LH) were studied in BALB/c mice. In a first experiment, performed in a lever press box, we observed that ICSS induced by brief (0.2 sec) electrical stimulation was enhanced by heptaminol. However, at the two doses administered (34.6 and 60 mg/kg), increases of the lever-pressing rate were observed only in animals showing high levels of performance before the treatment. In a second experiment, mice were trained in a shuttle-box to initiate and terminate a continuous stimulation of the LH. In animals showing a weak approach response before the treatment, heptaminol induced a significant reduction of approach latency but only at the dose of 60 mglkg. In contrast, animals showing a strong approach response appeared more sensitive to heptaminol since a reduction of approach latency was observed at the two doses administered. No concomitant modification of escape latency was observed. These results suggest 1) that heptaminol modulates activity of certain neuronal mechanisms involved in ICSS regulation and 2) that a relationship exists between the reactivity to heptaminol and the sensitivity of hypothalamic sites to electrical stimulation.