Arousal systems.

Recent advances in neural and behavioural pharmacology, and in intracellular recording suggest that arousal during the awake state may be regulated by multiple, interdependent neurotransmitter systems that originate in the brainstem or hypothalamus, and project to subcortical and cortical sites. We discuss efforts to determine the mechanisms by which these systems extent their effects, and the roles that they play in the control of arousal.

Alteration of brain noradrenergic activity in rhesus monkeys affects the alerting component of covert orienting.

Experiments were conducted to elucidate the role of the noradrenergic neurotransmitter system in arousal and the orienting of attention. Rhesus monkeys were trained to perform a peripherally cued, covert orienting task for juice reward, and their manual reaction times (RTs) to visual stimuli were measured. The effects of parenteral injections of the alpha-2 adrenergic agonists clonidine and guanfacine, and normal saline were compared on the covert task. We assessed 1) overall error rates, 2) the difference in RTs between validly and invalidly cued trials (validity effect), 3) the difference in RTs between neutral and no-cue trials (alerting effect), 4) target location (visual field), and 5) cue-target interval. Changes in noradrenaline levels produced by clonidine (and to a lesser extent guanfacine) significantly decreased the alerting effect, and lowered RTs to stimuli in the left visual field, but did not change the validity effect, suggesting that noradrenaline is involved in maintaining non-spatial, sensory readiness to external cues but not in the shifting of the attentional focus.

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance.

Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location). Reaction times (RTs) to the onset of the target were recorded. For monkeys, systemic injections of nicotine (0.003-0.012 mg/kg) or atropine (0.001-0.01 mg/kg), but not saline control injections, reduced mean RTs for all trials, indicating general behavioral stimulation. In addition, nicotine significantly reduced RTs for invalid trials but had little additional effect on those for valid, double, or no-cue trials. Virtually identical effects were observed for human chronic tobacco smokers in performing the same task following cigarette smoking. Injections of atropine in monkeys had no effect on RTs for valid or invalid trials but significantly slowed RTs in double-cue trials that did not require the orienting of attention. These results suggest that in both species, the nicotinic cholinergic system may play a role in automatic sensory orienting. In addition, the muscarinic system may play a role in alerting to visual stimuli in monkeys.

Visual orienting and alerting in rhesus monkeys: comparison with humans.

The behavioral capacities of the rhesus monkey for several sensory and cognitive tasks appear quite similar to those of humans. To evaluate the monkey's attentional capacities, we have compared monkey and human performance on a visuospatial attentional task, the cued target detection (CTD) paradigm. Animals were trained to fixate a small spot of light while a cue and a subsequent target, are flashed in the visual periphery. In valid trials, the cue and target appeared in the same spatial location; in invalid trials, the cue and target appeared in the opposite location; in double trials, two cues were presented and the target appeared in one of their locations; in no-cue trials, the cue was omitted and the target appeared in one location. In addition, we varied cognitive control over the task initiation by making the trial onset either self-paced or computer-paced. Reaction times (RTs) to target presentation, response accuracy, and frequency of aborted trials were measured for all subjects. No significant species differences were found for the patterns of RTs for different trial types or for attentional dynamics, as indexed by the decreases in RT with increasing cue-target interval. However, humans and non-human primates reacted differently to changes in cognitive control. Humans shows significant increases in no-cue trial RTs in the auto-paced task compared to the self-paced, but no differences in overall RT between tasks; monkeys showed a significant faster overall RT for the self-paced than the computer-paced task, but no difference between no-cue RTs. The performance differences between species may be related to the training history of the animals or to known anatomical differences in cortical organization, especially in the parietal lobe.

Pemoline produces ipsilateral turning behavior in unilateral 6-OHDA-lesioned rats.

1. Male Sprague-Dawley rats received either a unilateral injection of 6-hydroxy-dopamine or vehicle injection into the medial forebrain bundle. 2. Two weeks post surgery, all rats received a pemoline challenge (250 mg/kg s.c.), and rotational and stereotyped behaviors were videotaped and analyzed. 3. All rats regardless of injection expressed stereotyped behaviors and hyper-locomotion after pemoline challenge. 4. High performance liquid chromatography (HPLC) with electrochemical detection was used to evaluate changes in the levels of dopamine, serotonin and their metabolites in neostriata. 5. Rats with dopamine depleting lesions exhibited ipsilateral rotational behavior, indicating that pemoline, a central stimulant, is an indirect dopamine agonist in the rat. 6. The extent of dopamine depletion and serotonin elevation in the neostriatum in lesioned animals was related to the expression and degree of rotational behavior.