Microinfusion of clonidine and yohimbine into locus coeruleus alters EEG power spectrum: effects of aging and reversal by phosphatidylserine

Abstract

1 The behavioural and electrocortical (ECoG) power spectrum effects of clonidine, and yohimbine, an agonist and an antagonist at a2-adrenoceptors, after their unilateral microinfusion into the rat locus coeruleus (LC) in young (50-70 days old) and old (13-15 months old) rats were studied. 2 Clonidine (0.09, 0.19, 0.28 and 0.56 nmol) microinfused into the LC of young rats induced dosedependent behavioural and ECoG slow wave sleep (SWS) with a significant increase in total voltage power and power in the lower frequency bands. In contrast, yohimbine (1.3 and 2.6 nmol) infused into the LC of young rats produced ECoG desynchronization and a significant decrease in total voltage power. 3 In contrast to young rats, clonidine (0.19 and 0.28 nmol) given into the LC did not affect behaviour and the ECoG power spectrum in old rats. However, after higher doses of clonidine (0.56 and 1.2 nmol) a small and short-lasting period of behavioural and ECoG SWS was still evident. Similarly, in old rats yohimbine, at a dose (1.3 nmol) which was stimulative in young animals, did not significantly affect behaviour and ECoG power spectrum. Higher doses of yohimbine (2.6 and 5.2 nmol) were required to induce behavioural and ECoG changes similar to those observed with lower doses of yohimbine in young rats. 4 Chronic treatment with phosphatidylserine (30mgkg 1, orally, daily for 21 and 30 days), was able gradually to restore in old rats, in comparison with a vehicle-treated group, the responsiveness of a2-adrenoceptors to clonidine and yohimbine given into the LC.

Sleep and Human Aging

“…Older adult primates have fewer hypocretin/orexin-expressing axons that project to the sleep-wake regulating target of adrenergic centers in the locus coeruleus (LC) (Downs et al, 2007). Further implicating the adrenergic system, older rodents show less of the typical slow wave sleep increase in response to the α-2 adrenoreceptor agonist clonidine than younger rodents and less of the wake-promoting response to the antagonist yohimbine (de Sarro et al, 1988). However, whether these effects are also present in older adult humans is still unknown.…”

Noradrenergic modulation of wakefulness/arousal

“…Nonetheless, global suppression of LC-NE neurotransmission, using ICV or intrabrainstem-administered α 2 -agonists, potently decreases EEG/behavioral indices of arousal. 59, 60 The lack of sedative effects of bilateral MSA/MPOA β-receptor blockade likely reflects the wake-promoting actions of: 1) α 1 -receptors within these regions; and/or 2) α 1 - and β-receptors located outside these regions. In sum, in contrast to that observed in the presence of anesthesia, the wake-promoting actions of MSA β-receptors are not necessary for behavioral and EEG indices of alert waking even though stimulation of these β-receptors is sufficient to promote alert waking.…”

The locus coeruleus: A key nucleus where stress and opioids intersect to mediate vulnerability to opiate abuse

“…Certain physiological stimuli produce a more tonic activation of LC neurons and the stress neurohormone, CRF has been implicated in these responses (Kosoyan et al, 2005; Lechner et al, 1997; Valentino et al, 1991). Regardless of the stimulus, LC activation is sufficient to activate forebrain (e.g., cortex and hippocampus) EEG and selective LC inhibition has the opposite effect (Berridge and Foote, 1991; Berridge et al, 1993; Curtis et al, 1997; De Sarro et al, 1987; de Sarro et al, 1988; De Sarro et al, 1992; Page et al, 1992; Page et al, 1993). Moreover stress-elicited LC activation has been shown to be necessary for EEG activation by some stressors (Page et al, 1993).…”