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 μ, m lateral to LC. The alpha-adrenergic agonist clonidine (CLON), in concentrations ranging from 5–20 μM (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 μl of 0.02 M acetylcholine (ACh) produced a 3–4 min period of increased LC firing, with a l min latency to onset. Larger volumes (0.15 μl) 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[l–24] exhibited more complex effects, with an increase in discharge rate being accompanied by a decrease in action potential amplitude. The results obtained with adrenergic and cholinergic agents are compatible with previous observations based on systemic or iontophoretic administration of these substances. The effects of ACTH infusion are more complex, with local infusion of these substances producing electrophysiological effects different from those obtained with iontophoretic techniques. The robust, reliable effects of local infusion of cholinergic or adrenergic agents on LC activity which were obtained using the parameters described in this report imply that such injections produce a simultaneous, reversible, verifiable increase or decrease in the mean discharge rate of proportion of LC neurons. This method could be used to implement new strategies for examining the postsynaptic and behavioral effects of enhanced