Muscarinic receptors regulate striatal neuropeptide gene expression in normal and amphetamine-treated rats.

This study investigated the effects of pharmacological blockade or stimulation of muscarinic receptors on constitutive and amphetamine-stimulated preprodynorphin, substance P and pre-proenkephalin gene expression in rat striatum. Acute administration of the non-selective muscarinic antagonist, scopolamine (2.5, 5 and 10 mg/kg, s.

Intrastriatal injection of the metabotropic glutamate receptor antagonist MCPG attenuates acute amphetamine-stimulated neuropeptide mRNA expression in rat striatum.

In chronically cannulated rats, microinjection of a competitive metabotropic glutamate receptor (mGluR) antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), into the dorsal striatum at doses of 0.4, 2 and 10 micrograms/1 microliter did not affect basal levels of preprodynorphin, substance P and preproenkephalin mRNAs in the dorsal striatum as revealed by quantitative in situ hybridization. However, intrastriatal MCPG (0.

Scopolamine augments c-fos and zip/268 messenger RNA expression induced by the full D(1) dopamine receptor agonist SKF-82958 in the intact rat striatum.

It is generally accepted that the widely used, partial dopamine D(1) receptor agonist, SKF-38393, does not induce immediate early gene expression in striatal projection neurons unless D(1) receptors are sensitized and uncoupled from D(2) receptors by 6-hydroxydopamine lesions or reserpine treatment. In contrast, this study demonstrates, using quantitative in situ hybridization, that the full D(1) receptor agonist, SKF-82958, induced robust expression of c-fos and zif/268 messenger RNAs in the intact rat striatum, especially in the entire shell and medial and ventral core areas of the nucleus accumbens and olfactory tubercle, and in the cerebral cortex, 45 min after one injection. The induction of the striatal immediate early genes is characterized by (i) induction in only medium-sized spiny neurons, (ii) dose-dependent induction, which correlates well with dose-dependent increases in motor activity, and (iii) blockade by the D(1) receptor antagonist, SCH-23390.

D1 and D2 receptor regulation of preproenkephalin and preprodynorphin mRNA in rat striatum following acute injection of amphetamine or methamphetamine.

Our previous work has demonstrated a dose-dependent induction of striatal preprodynorphin (PPD) in response to a single injection of the psychostimulants amphetamine (AMPH) or methamphetamine (METH). In the present study, dose-response effects of acute administration of these stimulants on preproenkephalin (PPE) mRNA expression in the rat striatum were investigated with quantitative in situ hybridization histochemistry 3 h after injection. Acute AMPH or METH at equimolar doses (3.

Acute methamphetamine-induced zif/268, preprodynorphin, and preproenkephalin mRNA expression in rat striatum depends on activation of NMDA and kainate/AMPA receptors.

This study tested the role of N-methyl-D-aspartate and kainate/AMPA receptors in mediating mRNA expression of the immediate early gene zif/268 and the opioid peptide genes preprodynorphin and preproenkephalin in rat forebrain following a single injection of methamphetamine. At 3 h after acute methamphetamine [4 mg/kg, intraperitoneally (IP)], quantitative in situ hybridization histochemistry revealed that zif/268 mRNA expression was increased in the dorsal striatum (caudoputamen) and in the sensory cortex. Preprodynorphin was increased in both dorsal and ventral striatum (nucleus accumbens) and preproenkephalin was increased in the dorsal striatum.

The effects of D1 or D2 dopamine receptor blockade on zif/268 and preprodynorphin gene expression in rat forebrain following a short-term cocaine binge.

Selective D1 or D2 dopamine receptor antagonists were used to investigate the transynaptic regulation of mRNAs coding for the opioid peptide, preprodynorphin, and the nuclear transcription factor, zif/268 after an acute cocaine binge. Rats were injected intraperitoneally with the D1 receptor antagonist, SCH 23390, or the D2 receptor antagonist, sulpiride, 30 min prior to 3 hourly injections of saline or 20 mg/kg cocaine and killed 1 h after the final injection. Behavioral ratings indicated that SCH 23390 blocked, whereas sulpiride augmented, cocaine-induced stereotypical behaviors.

Differential effects of D1 and D2 dopamine receptor antagonists on acute amphetamine- or methamphetamine-induced up-regulation of zif/268 mRNA expression in rat forebrain.

This study investigated the hypothesis that D1 and D2 dopamine receptors interact to regulate the expression of zif/268 mRNA in rat forebrain after an acute injection of amphetamine or methamphetamine. Forty-five minutes and 3 h after a single injection of amphetamine (4 mg/kg i.p.

Repeated amphetamine administration induces a prolonged augmentation of phosphorylated cyclase response element-binding protein and Fos-related antigen immunoreactivity in rat striatum.

Semi-quantitative immunocytochemistry was used to investigate the levels of cyclase response element-binding protein, phosphorylated cyclase response element-binding protein, Fos and Fos-related antigen immunoreactivity in the striatum of rats after acute or repeated amphetamine administration. Rats were perfused 20 min (phosphorylated cyclase response element-binding protein) or 2 h (cyclase response element-binding protein, phosphorylated cyclase response element-binding protein, Fos, Fos-related antigen) after a single injection (5 mg/kg, i.p.

A single injection of amphetamine or methamphetamine induces dynamic alterations in c-fos, zif/268 and preprodynorphin messenger RNA expression in rat forebrain.

In this study, the effects of a single dose of the indirect dopamine agonists amphetamine and methamphetamine on behavior and messenger RNA expression were evaluated. Expression of c-fos, a member of the leucine zipper family, zif/268 (NGFI-A, egr1 and Krox-24), a member of the zinc finger family, and the opioid peptide, preprodynorphin, was investigated in various regions of rat forebrain with quantitative in situ hybridization histochemistry 1, 2, 3, 6 or 30 h after injection. Behavioral observations indicated that a qualitatively different behavioral syndrome was induced following methamphetamine (15 mg/kg, i.

Dose-dependent alteration in zif/268 and preprodynorphin mRNA expression induced by amphetamine or methamphetamine in rat forebrain.

The dose-related effects of a single injection of D-amphetamine (AMPH) or methamphetamine (METH) on the mRNA expression of the immediate early gene zif/268 and the opioid peptide preprodynorphin, in rat forebrain, were investigated with quantitative in situ hybridization histochemistry 3 h after injection. Both drugs at equimolar doses (3.75, 7.

Cocaine binges differentially alter striatal preprodynorphin and zif/268 mRNAs.

Several studies have demonstrated that cocaine increases preprodynorphin, c-fos, and zif/268 mRNAs in rat dorsal striatum. Multiple, closely spaced exposures to cocaine appear to elicit the greatest increases in dynorphin. However, the response of preproenkephalin, c-fos and zif/268 mRNAs to such a dosing regimen is unknown.

Alterations in striatal zif/268, preprodynorphin and preproenkephalin mRNA expression induced by repeated amphetamine administration in rats.

Quantitative in situ hybridization histochemistry was used to compare the effects of AMPH administration on mRNAs coding for zif/268, a member of the zinc finger family of immediate early genes, and the opioid peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in rat striatum after 3 dosing schedules: (1) acute; (2) once a day for 5 days, and (3) once a day for 5 days followed 10 days later by a challenge dose. Behavioral ratings indicated that the activity of rats was significantly higher after 5 daily AMPH (5 mg/kg, i.p.

Forskolin induces preproenkephalin and preprodynorphin mRNA in rat striatum as demonstrated by in situ hybridization histochemistry.

Cyclase response elements (CREs) are located in the promoter regions of several neuropeptide and immediate early genes. Activation of the adenylate cylase/cAMP second messenger cascade leads to phosphorylation of CRE-binding proteins (P-CREBs) which bind to CREs in the promoter regions of these genes and alter their rate of transcription. We have previously reported an increase in striatal immunoreactivity for P-CREB (phosphorylated on Ser-133) and Fos following intracerebroventricular (ICV) injection of H2O-soluble forskolin, a direct activator of adenylate cyclase.

Introduction to the role of excitatory amino acids in the actions of abused drugs: a symposium presented at the 1993 annual meeting of the College on Problems of Drug Dependence.

Recent evidence has demonstrated that N-methyl-D-aspartic acid (NMDA) and non-NMDA, excitatory amino acid (EAA) receptor antagonists block the motor stimulating, neurotoxic, and rewarding actions of cocaine and the amphetamines. The participants in this symposium discussed evidence that (i) the initiation of stimulant-induced behavioral sensitization involves NMDA receptor stimulation in the ventral tegmental area (VTA), (ii) competitive and non-competitive NMDA antagonists block the dopaminergic neurotoxic actions of methamphetamine, and (iii) NMDA receptor antagonists block cocaine and methamphetamine-induced increases in striatal neurotensin and dynorphin expression. Furthermore, a theoretical framework was proposed in which to interpret dopamine-glutamate interactions based on tonic and phasic dopamine release in the striatum under acute, chronic and withdrawal states of stimulant exposure.

Short-term cocaine self administration alters striatal gene expression.

Rats self-administered cocaine or received saline during 3 daily 5 h sessions and were euthanized 1 h after the final session. Quantitative in situ hybridization revealed that cocaine self-administration increased levels of preprodynorphin, but not preproenkephalin, c-fos, or zif/268 mRNAs in a patchy pattern in the dorsal striatum. These data demonstrate that the regulation of preprodynorphin gene expression is dissociable from that of c-fos and zif/268 in dorsal striatum following short-term cocaine self-administration.

NMDA receptors mediate amphetamine-induced upregulation of zif/268 and preprodynorphin mRNA expression in rat striatum.

The role of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors in D-amphetamine (AMPH)-induced behavioral changes and increased expression of the nuclear transcription factors, c-fos and zif/268, and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.

Role of kainate/AMPA receptors in induction of striatal zif/268 and preprodynorphin mRNA by a single injection of amphetamine.

The role of kainate/AMPA excitatory amino acid receptors in D-amphetamine (AMPH)-induced behavioral changes and the induction of immediate early gene and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.

Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs.

The effects of short- and long-term cocaine exposure on the expression of the nuclear transcription factor genes, c-fos and zif/268, as well as the opioid peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in various regions of rat brain were evaluated by injecting i.p. saline or 10, 20, or 30 mg/kg cocaine HCl once daily for 1 or 10 days.

Forskolin increases phosphorylated-CREB and fos immunoreactivity in rat striatum.

Promoter regions of the preproenkephalin, preprodynorphin, and c-fos genes contain cyclase response elements (CREs) as well as AP-1 sites. Activation of the adenylate cyclase cascade leads to phosphorylation of cyclase response element binding proteins (P-CREBs) which then bind CREs in these genes and induce transcription. In this experiment, semi-quantitative immunocytochemistry was used to examine striatal CREB-, P-CREB-, and Fos-like immunoreactivity (IR) 1 h following intracerebroventricular injection of H2O-soluble forskolin.