Noradrenergic modulation of sensorimotor processes in intact rats: The masseteric reflex as a model system

The masseteric jaw closure reflex was utilized as a model system with which to gauge the functional activity of central noradrenergic neurons. This system was chosen because it is a simple monosynaptic reflex the neuronal substrate of which receives a dense noradrenergic input. The modulatory effects of norepinephrine (NE) on this response in the intact, chloral hydrate-anesthetized rat were studied with a variety of pharmacological strategies. Initially, a reflex facilitation was obtained with the catecholamine precursor L-DOPA. Manipulations with greater specificity of action on the noradrenergic system were then employed. First, we used the presynaptic α-2 noradrenergic agonist clonidine, which acts to decrease noradrenergic transmission. Clonidine attenuated the amplitude of the reflex, and this suppression was blocked by pretreatment with the α-2 antagonist yohimbine. The effects of yohimbine itself were then examined, and a biphasic effect was obtained. At low doses, at which it preferentially acts as an antagonist at presynaptic α-2 receptors and increases noradrenergic transmission, yohimbine enhanced the reflex. At higher doses, at which it also displays postsynaptic α-1 antagonist activity, yohimbine depressed the reflex. This reflex modulation by yohimbine was blocked by pretreatment with the α-1 antagonist prazosin. The anatomical site of the observed effect was then localized to the direct noradrenergic innervation of the reflex circuitry by locally destroying, with 6-hydroxydopamine, the noradrenergic terminals in the trigeminal motor nucleus mediating the response. This significantly attenuated the reflex modulation by yohimbine, without affecting elicitation of the reflex itself. Thus, it was concluded that NE facilitates the masseteric reflex, and this facilitation is mediated directly by the noradrenergic input into the motor nucleus. To our knowledge, these represent the first studies to demonstrate modulation of a simple behavioral response by NE, at a specified site mediating that response, in intact animals. The relation of these studies to demonstrations of cellular modulation by NE is discussed.