Tonic inhibitory effect

Complex late adaptations occur upon repeated treatment with SSRIs, including indirect enhancement of NE output by reduction of tonic inhibitory effects of S-HT heteroreceptors. Finally, similar nuclear and cellular adaptations occur as with the tricyclic antidepressants, including increased intraneuronal cyclic AMP, activation/phosphorylation of transcription factors (e.g., CREB), and increased production of BDNF. 

This fall in both arterial pressure and cardiac filling leads to the activation of two different groups of pressure receptors, consisting of the high-pressure receptors of the carotid sinus and aortic arch and the low-pressure receptors of the heart and lungs (2). Within the heart there are mechanoreceptors linked by unmyelinated vagal afferents in all four cardiac chambers. These mechanoreceptors produce a tonic inhibitory effect on the cardiovascular control centers of the medulla. 

In conclusion, the distribution of NOS immunoreactivity and the pharmacological and physiological evidence analyzed and discussed here support the proposal that CB endogenous NO exerts a tonic inhibitory effect on CB chemoreception. Clearly, NO in low concentration is a broad inhibitory modulator of the chemoreception process in the CB. NO may modulate chemoreception by regulating the CB vascular tone, the oxygen delivery to the chemoreceptor cells, and the excitability of glomus cells and petrosal sensory neurons. 

Parkinsonism is unique among diseases of the CNS, in that it results from the known loss of a particular NT, i.e. DA, resulting from the degeneration of a particular pathway, the nigrostriatal. Dopamine also has a relatively limited distribution in the brain and few peripheral effects. It should therefore be amenable to therapy based on augmenting its function. Also since the role of DA appears to be to maintain a tonic inhibitory control on GABA output pathways from the striatum, possibly in part by an extra synaptic action (Chapter 6), it may not be necessary for it to be released physiologically from nerve terminals. Thus it may be adequate to just provide DA extracellularly. 

Furthermore, lack of Y1 receptor or antagonism at this receptor inhibited the antinociceptive potency of NPY at the spinal level. These data suggest that the Y1-receptor system exerts tonic inhibitory control and it mediates the antiallodynic effects of NPY during inflammatory and neuropathic pain syndromes. 

Since the early studies by Marks (1973) on the inhibitory effects of THC on pituitary luteinizing hormone (LH) secretion, a number of papers reported similar effects (Smith et al. 1980 Steger et al. 1980 Wenger et al. 1987). THC suppresses the tonic circulating level of LH in male rats (Chakravartyet al. 1982) and episodic LH secretion in female animals (Tyrey 1980). 

Prolactin is secreted in a pulsatile fashion by the lactotroph cells of the anterior pituitary, with the highest peak concentrations observed during sleep." The secretion of prolactin is regulated primarily by tonic hypothalamic inhibitory effects of dopamine. As described earlier in this chapter and listed in Table 75-1, many factors can affect prolactin secretion. During pregnancy, prolactin serum concentrations rise substantially above normal. All other conditions characterized by excess prolactin serum concentrations, known as hyperprolactinemia, are considered pathologic. 

The hallucinogen lysergic acid diethylamide (LSD) interacts with 5-HT, primarily through 5-HT2 receptors. When applied iontophoretically, LSD and 5-LLT both potently inhibit the firing of raphe (5-HT) neurons, whereas LSD and other hallucinogens are far more potent excitants on facial motoneurons that receive innervation from the raphe. The inhibitory effect of LSD on raphe neurons offers a plausible explanation for its hallucinogenic effects, namely that these effects result from depression of activity in a system that tonically inhibits visual and other sensory inputs. However, typical LSD-induced behavior is still seen in animals with destroyed raphe nuclei or after blockade of the synthesis of 5-HT by p-chlorophenylalanine. 

The cerebellum is responsible for the coordination of movement, and is composed of a cortex of gray matter, internal white matter, and three pairs of deep nuclei fastigial nucleus (FN), the interposed and globose nucleus, and dentate nucleus. The deep cerebellar nuclei and the vestibular nuclei transmit the entire output of the cerebellum. Output of the cerebellar cortex is carried through Purkinje cells. Purkinje cells send their axons to the deep cerebellar nuclei and have an inhibitory effect on these nuclei. The cerebellum is involved with both eye and head movements, and both tonic and phasic activities are reported in the cerebellum. The cerebellum is not directly responsible for the initiation or execution of a saccade, but contributes to saccade precision. Sites within the cerebellum important for the control of eye movements include the oculomotor vermis, FN and the flocculus. Consistent with the operation of the cerebellum for other movement activities, the cerebellum is postulated here to act as the coordinator for a saccade, and act as a precise gating mechanism. 

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