Effects of locally infused pharmacological agents on spontaneous and sensory-evoked activity of locus coeruleus neurons.

Electrophysiological activity of individual locus coeruleus (LC) neurons was recorded in halothane-anesthetized rats before, during, and after the infusion of adrenergic, cholinergic, or peptidergic compounds about 400 micron lateral to LC. The alpha-adrenergic agonist clonidine (CLON), in concentrations ranging from 5-20 microM (67-270 pg/50 nl injection), reversibly suppressed activity with latencies to onset of 5-15 min and durations of 20-120 min. During the onset of suppressed firing, responses to sensory stimuli (footshock) were relatively preserved, but at later times the reliability of footshock responses was greatly reduced. The alpha-adrenergic antagonist piperoxane (PIP) rapidly reversed the inhibitory effects of CLON. Infusion of 0.1 microliter of 0.02 M acetylcholine (ACh) produced a 3-4 min period of increased LC firing, with a 1 min latency to onset. Larger volumes (0.15 microliter) produced greater increases in firing rate lasting 10-12 min. ACh effects were readily reversed with equimolar doses of scopolamine (SCOP). The effects of 0.02 M ACh were also rapidly reversed by equal volumes of 0.001 M CLON, SCOP and CLON reduced basal firing rates without blocking responses to sensory stimuli. Infusion of the cholinergic agonist carbamyl-beta-choline (carbachol) produced robust, reliable activation of LC neurons at doses of 25-1,000 ng per 100 nl injection. The electrophysiological effects of 3 adrenocorticotropin hormone (ACTH) fragments [1-24], [4-10], and [1-10] were also evaluated. ACTH[1-10] and ACTH[4-10] decreased LC activity for up to 2 hr. ACTH[1-24] exhibited more complex effects, with an increase in discharge rate being accompanied by a decrease in action potential amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)