Dopamine and glutamate agonists stimulate neuron-specific expression of Fos-like protein in the striatum

Abstract

1. The monoamine dopamine and the amino acid glutamate are major neurotransmitters in the basal ganglia implicated in the normal functions of the striatum and in extrapyramidal disease states. To study the effects of these neurotransmitters on gene transcription in striatal neurons, we treated rats with dopamine (monoamine) agonists and with glutamate agonists and monitored the induction of Fos-like protein in striatal neurons. We administered the indirect monoamine agonists cocaine and amphetamine intraperitoneally and gave the glutamate agonist quinolinic acid by direct intrastriatal injection. We identified the phenotypes of the responsive neurons by immunohistochemistry and by enzyme histochemistry in double staining protocols. 2. Both the indirect monoamine agonists and the glutamate receptor agonist stimulated rapid nuclear expression of Fos-like protein in specific classes of striatal neurons. The induction by cocaine and amphetamine was blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390, and the induction by quinolinic acid was blocked by pretreatment with MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. 3. The monoamine and glutamate agonists both induced Fos-like protein exclusively in striatal neurons that constitutively expressed the protein phosphatase inhibitor DARPP-32 (dopamine and cAMP-regulated phosphoprotein). 4. The dopamine agonists failed to induce detectable Fos-like protein in striatal neurons expressing enkephalin, even though many such neurons expressed DARPP-32. By contrast, many enkephalinergic neurons did express Fos-like protein in response to glutamatergic stimulation. 5. Glutamate agonist stimulation, but not dopamine agonist stimulation, induced Fos-like protein in a subpopulation of striatal interneurons, namely, a group of neurons exhibiting NADPH-diaphorase activity. 6. These findings suggest that stimulation of dopamine D1-like receptors (or related monoamine receptors) and glutamate NMDA receptors activates neuron-specific programs of immediate-early gene expression in the striatum. Our findings further suggest that monoamine and glutamate may act cooperatively at the transcriptional level on a functionally defined subset of striatal neurons.

Differential spatial and temporal gene expression in response to axotomy and deafferentation following transection of the medial forebrain bundle

“…A similar gradient was seen both in the high-affinity dopamine uptake system demonstrated in the normal non-dopamine-depleted animal (Marshall et al, 1990) and in the levels of expression of D, receptors following 6-OHDA (Joyce,199 1). Interestingly, Graybiel and coworkers conclude from double labeling experiments that direct or indirect dopamine agonists do not induce c-fos-like proteins in the cholinergic intemeurons of the striatum (Graybiel, 1991;Berretta et al, 1992). The expression of c-fos in the CS cholinergic neurons following MFB transection may be related more to the consequences of the transection on the levels of CS dopamine than to the ability to activate specific dopamine receptor subtypes pharmacologically (see below).…”

“…Furthermore, both these experiments and those of other groups do not take into account the presence of other types of dopamine receptors reported in the striatum (Civelli, 199 1). Graybiel and colleagues also have shown that c-&s-positive neurons in the dopamine-depleted CS following acute cocaine and amphetamine treatment contain DARPP-32, a marker of the D, receptor, and that there is no C-$X response detectable in the GABA/enkephalin-containing neurons (Graybiel, 199 1;Berretta et al, 1992). The GABA/enkephalin-containing neurons project through an interneuron in the GP to the STN forming one branch of the subthalamic loop (Gerfen, 1992).…”

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…pathway neurons (Berretta et al, 1992;Cenci et al, 1992;Johansson et al, 1994;Kosofsky et al, 1995;Badiani et al, 1999), especially with higher doses (Uslaner et al, 2003;Ferguson et al, 2004) as used here. However, recent studies showed that factors such as novelty can enhance c-fos induction by psychostimulants also in the indirect pathway (Badiani et al, 1999;Uslaner et al, 2003;Ferguson et al, 2004).…”

Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson's disease?

“…23 This may be because amphetamine induces release of DA from nerve terminals via activation of the D1 receptor. 24,25 In rat striatum lesioned with 6-OHDA, the density of Fos-positive nuclei is lower than normal and can be restored by intrastriatal transplants of DA tissue. [26][27][28] We tested whether Ad-NSE-GDNF affected the release of DA by striatal fibers by injecting control rats (OHDA, empty-Ad) and Ad-NSE-GDNF-treated rats with amphetamine (5 mg/kg, i.p.).…”