NORADRENERGIC AGENTS INTO THE CEREBELLAR ANTERIOR VERMIS MODIFY THE GAIN OF VESTIBULOSPINAL REFLEXES IN THE CAT

The noradrenergic (NA) afferent projection to the cerebellar CorteX, which originates mainly from the locus coeruleus (LC), may act on the target neurons by utilizing both alpha- and beta-adrenoceptors. Experiments performed in decerebrate cats have shown that unilateral injection into the vermal cortex of the cerebellar anterior lobe of 0.25-mu-l of the alpha-1-adrenergic agonist metoxamine or the alpha-2-agonist clonidine (at 2-8-mu-g/mu-l of saline) as well as of the non-selective beta-agonist isoproterenol (at 8-16-mu-g/mu-l) decreased the postural activity in the ipsilateral forelimb, while the extensor tonus either remained unmodified or slightly increased on the contralateral side. The same agents also increased the gain of the vestibulospinal (VS) reflexes elicited by recording the multiunit EMG responses of the ipsilateral and the contralateral triceps brachii to roll tilt of the animal (at 0.15 Hz, +/- 10-degrees), leading to sinusoidal stimulation of labyrinth receptors. The crossed effects were more prominent for the alpha-2- than for the alpha-1- and beta-agonists. Only slight changes in the phase angle of the responses were observed. The effects described above appeared 5-10 min after the injection, reached the peak values after 15-30 min and disappeared within 2 h. The effective area was located within the third and/or the fourth folium of the culmen rostral to the fissura prima, 1.4-1.8 mm lateral to the midline. This area corresponded to zone B of the cerebellar cortex, which projects to the ipsilateral lateral vestibular nucleus (LVN), on which it exerts a prominent inhibitory influence. In fact, monopolar stimulation of this area with three negative pulses (at 300/sec) performed prior to the local injection inhibited the spontaneous EMG activity of the ipsilateral triceps brachii. The effects described above were dose-dependent: injection of an equal volume of saline was ineffective. All changes in posture and reflexes elicited by metoxamine or clonidine were impaired by previous injection into the same corticocerebellar area of the corresponding alpha-1- or alpha-2-adrenergic antagonist prazosin or yohimbine, respectively (0.25-mu-l at 8-16-mu-g/mu-l). However, cross-interactions between alpha-1- and alpha-2-adrenergic agonists and antagonists were also observed. In fact, injection of the alpha-2-adrenergic antagonist yohimbine prevented the occurrence of all the metoxamine effects, while administration of the alpha-1-adrenergic antagonist prazosin prevented the occurrence of the ipsilateral, but not of the contralateral effects induced by clonidine injection. In conclusion, while the ipsilateral effects induced by metoxamine and clonidine were almost equally depressed by the alpha-1- and the alpha-2-adrenergic antagonists, the contralateral effects were more prominently affected by the alpha-2, than by the alpha-1-antagonist. Injection in other experiments of 0.25-0.50-mu-l of the non-selective beta-adrenergic antagonist propranolol not only increased the extensor tonus in the ipsilateral limbs. while slightly reducing the extensor tonus in the contralateral limbs, but also decreased the response gain of the ipsilateral, and to a smaller extent of the contralateral, triceps brachii to animal tilt. The same injection also reduced or suppressed the postural and reflex changes induced by previous administration into the same corticocerebellar area of the non-selective beta-adrenergic agonist isoproterenol. An additional finding was that the propranolol injection slightly modified, but did not prevent, the increase in the response gain of the ipsilateral triceps brachii to labyrinth stimulation following administration into the same corticocerebellar area of the alpha-1- or the alpha-2-adrenergic agonist metoxamine or clonidine, while the contralateral effects (particularly induced by clonidine) were suppressed. These findings suggest differences in the degree of colocalization of alpha- and beta-adrenoceptors on the corticocerebellar neurons involved in the gain regulation of the ipsilateral and the contralateral triceps brachii to labyrinth stimulation. Since during animal till most of the Purkinje (P)-cells of the cerebellar vermis fire out-of-phase with respect to the related VS neurons, we postulated that both the alpha-1- and alpha-2-adrenergic agonists, as well as the beta-adrenergic agonist, act on these P-cells by enhancing the amplitude of their modulation to labyrinth stimulation, thus exerting a positive influence on the gain of the VS reflexes.