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 selective M4 muscarinic receptor toxin, MT3, was used in vivo to evaluate the role of M4 receptors in cholinergic inhibition of neuropeptide mRNA expression in striatonigral neurons. Unilateral injection of the muscarinic toxin 3 (0.04-4 nmol) into the dorsal striatum of chronically-cannulated rats elevated basal levels of preprodynorphin, substance P and preproenkephalin mRNAs in the ipsilateral dorsal striatum as revealed by quantitative in situ hybridization. Pretreatment with muscarinic toxin 3 also augmented amphetamine (2.5 mg/kg, i.p.)-stimulated preprodynorphin and substance P expression in the dorsal striatum in a manner similar to that observed after the muscarinic antagonist, scopolamine. Since muscarinic toxin 3 has a much greater affinity for muscarinic M4 receptors than for other subtypes, it is possible that muscarinic toxin 3, by interacting with the muscarinic M4 subtype, regulates basal and/or dopamine-stimulated striatal neuropeptide gene expression.
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PMID:The muscarinic toxin 3 augments neuropeptide mRNA in rat striatum in vivo. 934 26

It is established that dopamine (DA) controls the expression of preprodynorphin (PPDYN), preprotachykinin A (PPT-A) and preproenkephalin (PPE) mRNAs in striatal structures. Since cocaine, nicotine and ethanol enhance extracellular DA concentration, we have examined whether their repeated administration produced common changes in the expression of these mRNAs. Quantitative in situ hybridization histochemistry was performed in rats 2 h after a final challenge subsequent to repeated subcutaneous injections (3 X a day) of cocaine (12.5 mg/kg), nicotine (0.4 mg/kg) for 14 days and ethanol (160 mg/kg) for 7 days. In the dorsal striatum, cocaine produced simultaneous PPDYN and PPT-A mRNA increases without PPE mRNA change whereas nicotine and ethanol produced no modification. After cocaine, PPDYN mRNA was preferentially increased in striatal patch compartment. In the nucleus accumbens, the effects were more complex. In cocaine-treated rats, we measured concomitant increases of PPDYN and PPE mRNA in the rostral pole, an isolated induction of PPT-A mRNA signals in the core without any change in the two shell subregions: the cone and the ventral shell. In contrast, after nicotine and ethanol, the ventral shell was the only accumbal subregion which showed a neuropeptide mRNA alteration, nicotine leading to decreased PPDYN mRNA and ethanol to increased PPT-A mRNA contents. The neuropeptide regulation after chronic treatment with these psychostimulant drugs does not strictly conform to a general DA control scheme in the dorsal and the ventral striatum. The cocaine effects can be clearly distinguished from those of nicotine and ethanol in terms of neuropeptide regulation and striatal subregions affected.
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PMID:Repeated administration of cocaine, nicotine and ethanol: effects on preprodynorphin, preprotachykinin A and preproenkephalin mRNA expression in the dorsal and the ventral striatum of the rat. 952 67

Metabotropic glutamate receptors (mGluR) are coupled to multiple intracellular second messenger systems through G-proteins and densely expressed by medium spiny projection neurons in the rat striatum. Unlike ionotropic glutamate receptors which mediate rapid synaptic transmission, mGluRs are important for relatively long-lasting modulation of neuronal metabotropic activity, possibly including gene expression, in response to cellular stimulation. In this study, the effects of acute injection of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on behavior and striatal neuropeptide mRNA expression were evaluated in chronically-cannulated rats. Unilateral injection of ACPD into the dorsal striatum at doses of 0.8, 4, 20, 100, 500 and 1000 nmol had no significant effect on spontaneous behavioral activity. However, intrastriatal ACPD (0.8, 4, 20 and 100 nmol) dose-dependently elevated preprodynorphin (PPD), substance P (SP) and preproenkephalin (PPE) mRNA expression in the dorsal striatum as revealed by quantitative in situ hybridization. PPD/SP mRNAs showed a biphasic response to a single injection of ACPD as the expression of these two mRNAs was increased at 3 and 6 h, decreased at 11 h, and returned to normal 24 h after ACPD administration. PPE induction in the dorsal striatum was significantly elevated as early as 2 h and remained even 24 h after ACPD was injected. In addition, the PPD and PPE mRNA induction by ACPD was blocked by intrastriatal pretreatment with the selective mGluR antagonist, (+)-alpha-methyl-4-carboxyphenyl-glycine. These data demonstrate a facilitatory regulation of constitutive expression of striatonigral PPD/SP, and striatopallidal PPE, mRNAs by local mGluR-mediated glutamatergic transmission.
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PMID:Metabotropic glutamate receptor agonist increases neuropeptide mRNA expression in rat striatum. 955 48

To investigate the effects of type I (mineralocorticoid) and type II (glucocorticoid) receptor activation on striatal neuropeptide [preproenkephalin (PPE), preprotachykinin (PPT), and preprodynorphin (DYN)] mRNA and midbrain cholecystokinin (CCK) mRNA as well as striatal tyrosine hydroxylase radioimmunoreactivity (TH-RIC) levels, we administered either replacement levels of corticosterone (CORT; 0.5 mg/kg/day, s.c.) or pharmacological levels of deoxycorticosterone acetate (DOCA; a mineralocorticoid steroid with ability to bind to type I and type II receptors; 5 mg/kg, s.c.) to adrenalectomized adult male rats. After 1 week of recovery from adrenalectomy surgery, animals were injected daily with sesame oil or CORT for 1, 3, or 7 days or DOCA for 3 or 7 days and killed 16 h after the last injection. Adrenalectomy resulted in a decrease in all three striatal neuropeptide mRNA levels, compared with sham-operated rats. CORT replacement resulted in recovered PPE and PPT mRNA levels after 1 day and elevated PPE mRNA levels over those in sham-operated controls after 3 days. In contrast, DYN mRNA levels showed recovery after 7 days of CORT replacement. Results after DOCA treatment largely paralleled those after CORT replacement. There were no significant treatment effects on indirect markers of midbrain dopaminergic activity, i.e., CCK mRNA and TH-RIC. From these results we conclude that compared with striatal tachykinin and dynorphinergic neurons, enkephalinergic cells show greater sensitivity, whereas the dopaminergic system, including mesencephalic CCK, demonstrates an insensitivity to physiological CORT and to pharmacological DOCA treatment.
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PMID:Effects of adrenal steroids on basal ganglia neuropeptide mRNA and tyrosine hydroxylase radioimmunoreactive levels in the adrenalectomized rat. 968 76

Rats exposed to a low-light, low-noise, novel environment exhibit differences in individual locomotor response to the novelty stressor. The categorization of rats in a locomotor screening procedure as low- (LR) or high-responders (HR), where LRs are in the low locomotor range while HRs belong to the high locomotor range, is significant in that HRs show higher activity in mesencephalic dopaminergic projection neurons, and also show a higher propensity to self-administer psychostimulants and other drugs of abuse compared with LRs. In this study, we examined the neurobiological basis of dopaminergic hyperactivity by comparing in HRs and LRs the steady-state differences in regulatory inputs to mesencephalic (substantia nigra and ventral tegmental area: VTA) dopaminergic neurons. In particular, using in situ hybridization, we studied levels of mRNA for tyrosine hydroxylase (TH) and cholecystokinin (CCK) in the mesencephalon, and for preprodynorphin (DYN), preproenkephalin (PPE), and preprotachykinin (PPT) in the striatum and nucleus accumbens (Acb). We also evaluated TH levels by radioimmunocytochemistry (TH-RIC) in striatal, accumbal and mesencephalic regions. HRs versus LRs had lower levels of neurochemicals belonging to the intrinsic inhibitory input to dopaminergic neurons in the VTA, e.g. lower TH-RIC (-25%) and CCK-mRNA (-48%). In contrast, HRs showed higher levels of parameters belonging to extrinsic facilitating inputs, e.g. higher PPE-mRNA (+37%). In addition, HRs had higher DYN-mRNA in Acb (+61%), which has been shown to be positively correlated with higher dopaminergic activity. These results enhance our knowledge of the neurobiological correlates of individual rats' propensities to develop drug-intake and provide some putative mechanisms for the dopaminergic hyperactivity that characterizes drug-prone animals.
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PMID:Neurochemical characterization of individual vulnerability to addictive drugs in rats. 978 9

The purpose of this study was to investigate whether GABA(A) receptors in the dorsal striatum regulate basal or stimulant-induced behaviors. Correspondingly, the question of possible GABA(A) receptor control of neuropeptide mRNA expression in nigrostriatal neurons was addressed. The GABA(A) receptor antagonist, bicuculline, was unilaterally or bilaterally microinjected into the dorsal striatum of rats in a series of 3 studies. In the first study, unilateral administration of 10-50 ng/microliter of bicuculline did not alter behavior. However, 250 ng/microliter bicuculline produced motor dyskinesias and/or seizures. In the second study, 100 ng/microliter bicuculline administered unilaterally prior to saline or amphetamine treatment, produced mild twitching in 61% of rats but did not affect amphetamine (2.5 mg/kg, i.p.)-induced behavioral activity, specifically rearing and sniffing. In the third study, 75 ng/microliter of bicuculline was administered unilaterally or bilaterally into the striatum in two separate experiments. Administration of bicuculline either unilaterally or bilaterally produced mild transient twitching of the forelimbs but did not affect behaviors induced by the selective D(1) receptor agonist SKF-82958 (0.5 mg/kg, s.c.). Three hours after unilateral bicuculline administration, the brains were removed and processed for quantitative in situ hybridization. Bicuculline did not significantly affect the basal or SKF-82958-induced increase in preprodynorphin or substance P mRNA expression in striatonigral neurons on the side of injection. These data suggest that blockade of GABA(A) receptors in the dorsal striatum does not affect dopamine agonist-stimulated behaviors or neuropeptide mRNA expression in striatonigral neurons in the rat striatum.
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PMID:The role of dorsal striatal GABA(A) receptors in dopamine agonist-induced behavior and neuropeptide gene expression. 1041 9

Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.
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PMID:Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates. 1053 May 7

Group I metabotropic glutamate receptors (mGluRs) are positively coupled to phosphoinositide hydrolysis through G-proteins and are densely expressed in the medium-sized spiny neurons of striatum. Activation of this group of mGluRs in the striatum produces long-lasting stimulation of behavioral activity. In this study, the role of group I mGluRs in the modulation of neuropeptide mRNA expression in striatal neurons was investigated using a Group I-selective agonist, 3,5-dihydroxyphenylglycine (DHPG) in chronically cannulated rats. Unilateral injections of DHPG into the dorsal striatum (caudoputamen) at behaviorally active doses of 20, 40, and 80 nmol elevated basal levels of preprodynorphin (PPD), substance P (SP), and preproenkephalin (PPE) mRNAs in the injected dorsal striatum as revealed by quantitative in situ hybridization. The elevation of all three mRNAs was dose-dependent and the responsiveness of opioid peptide mRNAs (PPD and PPE) to acute injection of DHPG at each dose surveyed was greater than that of SP mRNA. Induction of the mRNAs was delayed and prolonged as increases in hybridization signal became evident at 2 (SP and PPE) or 3 (PPD) h, reached a peak between 3 and 6 h, and returned to normal levels 24 h after DHPG injection. Coadministration of a Group I-selective antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carbo xamide (PHCCC, 10 nmol), with DHPG markedly attenuated DHPG-stimulated PPD, PPE, and, to a lesser extent, SP expression. Administration of PHCCC alone had no significant effect on basal levels of three mRNA expression in the striatum. This study provides a detailed description of the dose- and time-related alterations in striatonigral PPD/SP and striatopallidal PPE mRNA expression in response to a single injection of the Group I agonist DHPG. Data obtained demonstrate a facilitatory, dynamic regulation of constitutive expression of PPD, SP, and PPE mRNAs by local enhancement of glutamatergic tone on DHPG- and PHCCC-sensitive Group I mGluRs.
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PMID:Selective activation of group I metabotropic glutamate receptors upregulates preprodynorphin, substance P, and preproenkephalin mRNA expression in rat dorsal striatum. 1107 13

The abuse of psychostimulants, such as methamphetamine (METH), can cause long-lasting deficits in the dopamine (DA) innervation of the striatum. Although the consequences of large DA depletions on basal ganglia function have been well characterized, less is known about the alterations associated with smaller depletions, such as those produced by high doses of METH. The purpose of this study was to assess the long-term consequences of METH-induced DA depletion on basal ganglia function. Three weeks after rats were given multiple administrations of METH (5-10 mg/kg, four times at 2-h intervals), dose-related decreases in DA tissue content in striatum and tyrosine hydroxylase mRNA in the substantia nigra pars compacta were observed. In situ hybridization histochemistry revealed a selective decrease in preprotachykinin mRNA in striatum, predominantly at the highest dose of METH, and no change in striatal preprodynorphin, preproenkephalin, or neurotensin/neuromedin N mRNAs. Cytochrome oxidase activity was significantly elevated in the entopeduncular nucleus and substantia nigra pars reticulata of METH-treated rats, but not in the striatum, globus pallidus, or subthalamic nucleus, consistent with a selective decrease in striatonigral, but not striatopallidal, neuron function. Additionally, rats treated with a neurotoxic regimen of METH were impaired on a radial maze sequential learning task when tested 3 weeks following METH administration. These data indicate that exposure to a neurotoxic regimen of METH results in long-term changes in striatonigral, but not striatopallidal neuron function and, consequently, altered basal ganglia function.
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PMID:Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine. 1116 Jun 39

The purpose of this study was to investigate the role that kappa opioid receptor stimulation has upon stimulant-induced behavior and neuropeptide gene expression in the striatum. Acute administration of amphetamine (2.5 mg/kg i.p.) caused an increase in behavioral activity and preprodynorphin, substance P, and preproenkephalin mRNA expression. When amphetamine-treated rats were pretreated with U69593, a kappa agonist (0.16 or 0.32 mg/kg s.c.), there was a significant decrease in behavioral activity. Quantitative in situ hybridization histochemistry revealed that 0.32 mg/kg U69593 significantly decreased amphetamine-induced mRNA expression of all three neuropeptides; however, only the induction of preproenkephalin mRNA was decreased by 0.16 mg/kg. These data suggest that stimulation of kappa receptors decreases acute amphetamine-induced behavior and mRNA expression of neuropeptides in the rat striatum.
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PMID:Kappa opioid receptor stimulation decreases amphetamine-induced behavior and neuropeptide mRNA expression in the striatum. 1153 35


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