Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to characterize the nature of the behavioural response to substance P (SP) infusion into the substantia nigra and to evaluate this response in 6-hydroxydopamine (6-OHDA) caudate lesioned rats. The effects of SP infusions (3 microgram in 1 microliter bilaterally) were assessed in an open field. Two groups of rats were used: one with 6-OHDA lesions in the caudate nucleus, and one with sham lesions. In sham rats, the first infusion produced a strong increase in sterotyped rearing and sniffing, with no concurrent enhancement of locomotion. With three subsequent infusions (made at interval of two days) the rearing response disappeared and a tendency to groom emerged. All SP-induced behavioural stimulation was blocked in the caudate-lesioned rats; an effect of the lesion itself was reduced rearing. These results suggest that the response to SP infusion is mediated through the nigro-striatal dopamine system. The behavioural profiles which emerge after SP infusion into the substantia nigra and ventral tegmental area are compared. In general, the behavioural studies of SP effects support the concept that the A9 and A10 dopamine systems can be behaviourally differentiated.
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PMID:Substance P infusion into substantia nigra of the rat: behavioural analysis and involvement of striatal dopamine. 9 50

The functional role of the putative transmitter substance P (SP) was studied using a behavioural approach. SP infusion into the ventral tegmental area in awake rats elicited an increase in locomotor activity which could be blocked by either infusion of a neuroleptic into the nucleus accumbens septi (NAS) or by 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic A10 neurones. Our results suggest that SP induces its behavioural effects through activation of dopaminergic A10 neurones, and imply that endogenous SP may have an important modulatory role.
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PMID:Behavioural activation induced in the rat by substance P infusion into ventral tegmental area: implication of dopaminergic A10 neurones. 51 44

The locomotor activity (LMA) response induced after infusion of selective neurokinin (NK) agonists into the cell body (A10) and a terminal region of the mesolimbic pathway of the rat was investigated. Infusion of the NK1 receptor-selective agonist, GR73632, into the ventral tegmental area (VTA: A10) or the nucleus accumbens (NAS) significantly and dose-dependently increased basal LMA. Agonists selective for the NK2 and NK3 receptors, GR64349 and senktide respectively, had no effect on LMA after intra-NAS infusion. The LMA induced by GR73632 is mediated via dopamine (DA) since the response was abolished by haloperidol. From these studies it would appear that the elevated LMA reported previously after VTA or NAS administration of substance P probably occurs via NK1 receptors. Such data supports the notion that endogenous NKs are likely to be important in modulating the mesolimbic DA pathway and, as a consequence, compounds which antagonise their effects could be useful for the treatment of disorders associated with this system. However, simultaneous infusion of the NK1 agonists, +/- CP-96,345 and its analogue CPQ, into the VTA did not attenuate the LMA induced after intra-VTA infusion of GR73632. Co-infusion of the NK1 antagonist CPQ, but not +/- CP-96,345, attenuated the LMA response induced by GR73632 in the NAS. The apparent poor susceptibility of these responses to blockade by the recently developed non-peptide NK1 antagonists was unexpected but may reflect their poor affinity for the rat variant of the NK1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the rat mesolimbic dopamine pathway by neurokinins. 128 18

Using a double-immunostaining technique with cholera toxin (CT) as a retrograde tracer, the authors examined the cells of origin and the histochemical nature of lower brainstem afferents to the cat posterior hypothalamus. The posterior hypothalamus, in particular the lateral hypothalamic area, receives substantial afferent projections from: substantia nigra, peripeduncular nucleus, ventral tegmental area, periaqueductal grey, mesencephalic reticular formation, peribrachial region including the locus coeruleus complex, rostral raphe nuclei and the rostral part of the nucleus magnus. In addition, a moderate number of retrogradely labeled neurons was found in: Edinger-Westphal nucleus, nucleus reticularis pontis oralis, nucleus reticularis magnocellularis, caudal lateral bulbar reticular formation around the nucleus ambiguus and lateral reticular nucleus and the nucleus of the solitary tract. The posterior hypothalamus receives: 1) dopaminergic inputs from A8, A9 and A10 cell groups; 2) noradrenergic inputs from A6 and A7 pontine, as well as A1 and A2 bulbar cell groups; 3) adrenergic inputs from C1 cell group in the caudal medulla; 4) serotoninergic inputs from the rostral raphe nuclei (B6, B7 and B8 cell groups); 5) cholinergic inputs from the peribrachial region of the dorsal pontine tegmentum as well as from the nucleus reticularis magnocellularis of the medulla; 6) peptidergic inputs such as methionine-enkephalin, substance P, corticotropin-releasing factor and galanin that originate mainly in the mesencephalic periaqueductal grey, the dorsal raphe nucleus and the peribrachial region of the dorsal pontine tegmentum.
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PMID:Lower brainstem afferents to the cat posterior hypothalamus: a double-labeling study. 197 Sep 46

A comparison was made between substance P (SP) and substance K (SK) in the ventral tegmental area (VTA) (A10 dopamine cell group) of the rat. Approximately equal densities of SP and SK-immunoreactive neuronal fibers were observed. However, while previous reports demonstrate negligible density of autoradiographically defined SP receptors in the VTA, we observed a high density of SK receptors. SK or SP was microinjected into the VTA, and changes in spontaneous motor activity were measured using a photocell apparatus. SK was found to be at least 10 times more potent than SP in producing an increase in motor activity. These data suggest that while both SK and SP are present in the VTA, SK may have a more significant physiological role in modulating dopamine neurons in the ventromedial mesencephalon.
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PMID:Substance K and substance P in the ventral tegmental area. 241 93

Cholecystokinin (CCK), enkephalin, neurotensin (NT), substance P (SP) and substance K (SK) are five neuropeptides that exist in neuronal perikarya or fibers in the vicinity of the A10 dopamine neurons in the ventromedial mesencephalon. Based upon this anatomical proximity, many investigations have been evaluating the possibility that these peptides may influence the function of the A10 dopamine neurons. A variety of experimental techniques have been employed in this regard, including anatomical, electrophysiological, neurochemical and behavioral methodologies. Measurement of immunoreactive peptide levels with radioimmunoassay, and visualization of peptidergic neurons and fibers with immunocytochemistry has demonstrated not only that peptides exist in the vicinity of A10 dopamine neurons, but using double labeling techniques NT and CCK have been found to coexist with dopamine in the same neuron. Further, by combining retrograde tracing technique with immunocytochemistry, the origin of some peptidergic afferents to the ventromedial mesencephalon has been determined. With the exception of CCK-8, microinjection into the ventromedial mesencephalon of rats with all the peptides or potent analogues produces a dose-related increase in spontaneous motor activity. For SP, NT and enkephalin the motor response has been blocked by dopamine antagonists. Further, an increase in dopamine metabolism in mesolimbic dopamine terminal fields is produced concurrent with the behavioral hyperactivity. These data indicate that SP, SK, enkephalin and NT can activate dopamine neurons in the ventromedial mesencephalon. This postulate is supported by electrophysiological studies showing an excitatory action by iontophoretic administration of peptide onto dopamine neurons. However, in some studies, excitatory electrophysiological effects were not observed. While some observations are contradictory, sufficient data has accumulated that tentative postulates and conclusions can be made about how these peptides may influence the A10 dopamine neurons. Further, speculations are offered as to the role this modulatory action may play in the many behaviors and pathologies thought to involve these dopamine neurons.
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PMID:Interactions between neuropeptides and dopamine neurons in the ventromedial mesencephalon. 241 73

The neuropeptides substance P, neurotensin and [Met]enkephalin are found in the ventral tegmental area, site of the A10 dopamine cell bodies. Evidence suggests a functional interaction between these peptides and the dopaminergic neurons. All three peptides have been shown to exert an activating effect on these neurons. The present study analyzed the effects of ventral tegmental area infusion of neurotensin, substance P and D-ala-[Met]enkephalin on feeding behavior. These effects were studied in both food-deprived and satiated rats. During a 30 min test, the following parameters were registered: latency to eat, total food intake, food spillage, number of eating bouts and duration of eating. Similar measures were taken for drinking. In deprived rats substance P (0.5, 3.0 micrograms) increased latency to eat but did not affect other parameters, and substance P did not affect eating in satiated rats. Neurotensin (0.5, 2.5 micrograms) increased latency to eat and markedly reduced food consumption in deprived rats and had no effect in satiated rats. D-Ala-[Met]enkephalin (0.1, 1.0 micrograms) stimulated feeding behavior in both deprived and satiated rats. These results show that although the different peptides are presumed to activate the dopaminergic A10 neurons, their effects on feeding behavior can be differentiated. The findings are discussed in terms of motor and motivational mechanisms, and the relative contributions of specific and non-specific influences on feeding are considered.
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PMID:Ventral tegmental area infusion of substance P, neurotensin and enkephalin: differential effects on feeding behavior. 242 71

Neurokinin-alpha (NKA) and substance P (SP), neuropeptides of the tachykinin family, have been identified in dopaminergic areas of rat brain. It has previously been shown that SP microinjected into the ventral tegmental area (VTA), site of the dopaminergic A10 (DA-A10) cell bodies, causes a behavioral activation characteristic of dopamine agonists. The present experiment measured open field behavior following bilateral VTA injections of NKA (0.02, 0.2, 2.0 micrograms/0.5 microliters). NKA induced a dose-dependent behavioral activation at lower concentrations of NKA than previously reported with SP. Medium and high doses of NKA produced significant increases in locomotion and rearing in both the center and periphery of the open field. Grooming decreased with dose, although this effect was not significant. In a second experiment, the behavioral activation by NKA (2.0 micrograms) was blocked by pretreatment with haloperidol (0.2 mg/kg), confirming that the NKA-induced effect is mediated by dopamine. Although the VTA contains both SP and NKA, receptors binding NKA exist here in greater density than those binding SP. Thus NKA may be the tachykinin in this region that preferentially interacts with DA-A10 neurons mediating behavioral arousal.
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PMID:Neurokinin-alpha injected into the ventral tegmental area elicits a dopamine-dependent behavioral activation in the rat. 246 85

The neuropeptides neurotensin, substance P, neurokinin-alpha (substance K), and met-enkephalin are present endogenously in the ventral tegmental area (VTA), site of the A10 dopaminergic (DA) cell bodies. In the present study these four peptides were injected bilaterally into the VTA in the rat, and the effects on operant behavior were assessed. Cannulae aimed at the VTA were implanted in four groups of animals, which had been trained to bar-press for food reward on a fixed-interval, 40-s schedule. A fifth group, in which the effects of systemically administered amphetamine were assessed, was also tested. Response rate across the interval was measured, and the index of quarter-life was taken as an indication of the temporal pattern of responding. In addition, a rate-dependency analysis was carried out for all data. Neurotensin (NT, 0.0175, 0.175, 0.5 micrograms in 1 microliter) dose-dependently decreased response rates without affecting quarter-life, and reduced the number of reinforcements obtained. Substance P (SP, 0.1, 1.0, 3.0 micrograms) did not affect responding, and neurokinin-alpha (NKA, 0.1, 1.0, 3.0 micrograms) induced a small increase in responding. Quarter-life was not affected by SP or NKA, but responding on the non-reinforced lever was significantly increased by both peptides. d-Ala-met-enkephalin (DALA, 0.01, 0.1, 1.0 micrograms) induced a dose-dependent increase in responding which was also rate-dependent, and reduced quarter-life. DALA effects were similar to the classic pattern of responding observed after systemic amphetamine. These results suggest that although all these peptides elicit behavioral activation and may affect DA neuronal activity, the behavioral responses can be differentiated with respect to operant behavior.
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PMID:Neurotensin, substance P, neurokinin-alpha, and enkephalin: injection into ventral tegmental area in the rat produces differential effects on operant responding. 247 Dec 21

Neurotransmitter-related messenger RNAs were detected by in situ hybridization in sections of rat and mouse brains by using 35S-radiolabelled RNA probes transcribed from cDNAs cloned in SP6 promoter-containing vectors. The distribution of messenger RNAs for glutamic acid decarboxylase, tachykinins (substance P and K), and tyrosine hydroxylase was examined in the striatum, pallidum, and substantia nigra. Dense clusters of silver grains were observed with the RNA probe complementary of the cellular messenger RNA for glutamic acid decarboxylase (antisense RNA) over most large neurons in the substantia nigra pars reticulata and medium-sized to large neurons in all pallidal subdivisions. A few very densely and numerous lightly labelled medium-sized neurons were present in the striatum. Among the areas examined, only the striatum contained neurons labelled with the antisense tachykinin RNA. Most of these neurons were of medium size, and a few were large. With the antisense tyrosine hydroxylase RNA, silver grains were found over neurons of the substantia nigra pars compacta and adjacent A10 and A8 dopaminergic cell groups. No signal was observed with RNAs identical to the cellular messenger RNA for glutamic acid decarboxylase or tachykinin (sense RNA). These results show a good correlation with immunohistochemical studies, suggesting that documented differences in the distribution and the level of glutamic acid decarboxylase, tyrosine hydroxylase, and substance P immunoreactivities in neurons of the basal ganglia are related to differences in the level of expression of the corresponding genes rather than to translation accessibility, stability, or transport of the gene products.
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PMID:Comparative distribution of mRNAs for glutamic acid decarboxylase, tyrosine hydroxylase, and tachykinins in the basal ganglia: an in situ hybridization study in the rodent brain. 288 96


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