P.2.d.026 Chronic administration of quetiapine increases norepinephrine and serotonin neurotransmission in the rat brain

Abstract

Experiments performed in precollicular decerebrate cats have shown that dorsal pontine structures, including the LC and the related dorsal pRF, play an important role not only in the control of posture but also in the gain regulation of the VS reflexes. The LC neurons, which are not only noradrenergic but also NE-sensitive due to the existence of self-inhibitory synapses acting on a2-adrenoceptors, send inhibitory afferents to the dorsal pRF; on the other hand, these pontine reticular neurons, which are presumably cholinergic as well as cholinoceptive due to the existence of self-excitatory synapses, project excitatory afferents to the medullary inhibitory RS system. The increased discharge of these pontine reticular neurons and the related inhibitory RS neurons following local injection of cholinergic agonists into the dorsal pRF decreased the postural tonus in the ipsilateral limbs but greatly enhanced the amplitude of the EMG modulation and thus the response gain of ipsilateral limb extensors to labyrinth stimulation. This finding did not depend on the decreased postural activity, since it was still observed when the EMG activity was reflexly maintained by an increased static stretch of the muscle. Similar results were also obtained when the discharge of the pontine reticular neurons and the related inhibitory RS neurons was raised after local injection of an a2-adrenergic agonist into the LC, leading to functional inactivation of the noradrenergic LC neurons. On the other hand, an increased postural activity in the ipsilateral limbs as well as a reduced gain of the corresponding VS reflexes were obtained when the discharge of the pontine reticular neurons and the related inhibitory RS neurons was reduced, as shown after local injection of cholinergic agonists into the LC leading to activation of the noradrenergic neurons. There was also evidence that cholinergic excitatory afferents to the LC originated from the ipsilateral dorsal pRF. The effects described above were dose-dependent as well as site-specific, as shown by histological controls. In conclusion, the pontine structures described above operate as a variable-gain regulator acting at the motoneuronal level during the VS reflexes. Since the same structures are also responsible for the spontaneous fluctuations in posture related to the sleep waking cycle, they may well intervene as a control system in order to adapt to the animal state the response gain of limb extensors following labyrinth stimulation.