Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum.

Fuxé, Kjell; O’Connor, William T.; Antonelli, Tiziana; Osborne, Peter G.; Tanganelli, Sergio; Agnati, Luigi F.; Ungerstedt, Urban

doi:10.1073/pnas.89.12.5591

Cited by 72 publications

(40 citation statements)

References 34 publications

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“…They provide direct in vivo evidence for a specific action of c-fos antisense oligonucleotides on striatonigral GABA neurons, since the striatopallidal pathway is unaffected by the c-fos antisense oligonucleotide. Recent microdialysis studies provided a positive control for this effect by demonstrating that pallidal GABA release decreases after intrastriatal perfusion with the DA D 2 receptor agonist pergolide (34,38).…”

Section: Discussionmentioning

confidence: 99%

Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal γ-aminobutyric acid transmission in the conscious rat

Sommer

Rimondini

O’Connor

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Antisense c-fos oligonucleotides injected into the neostriatum of conscious rats selectively inhibited c-fos expression associated with compensatory increases in striatal c-fos mRNA levels and also with increased expression of junB and NGFI-A mRNA, probably as a result of regulatory phenomena. Dual probe in vivo microdialysis was used to investigate ␥-aminobutyric acid (GABA) release in the substantia nigra and the globus pallidus, which represent the terminal sites of the dopamine D 1 receptor regulated striatonigral and the dopamine D 2 receptor regulated striatopallidal GABA pathways, respectively. Intrastriatal infusion of the c-fos antisense oligonucleotide profoundly decreased dialysate GABA levels in the ipsilateral substantia nigra within 60 min but did not inf luence the dialysate GABA levels in the globus pallidus compared with the sham and control oligonucleotide treated groups. The site of action of the antisense oligonucleotides was mainly restricted to striatal neurons as shown by the distribution of locally injected f luoresceine isothiocyanate and radiolabeled oligonucleotides. The findings demonstrate a facilitatory role for c-fos mediated gene regulation in striatonigral GABA transmission and strengthen the evidence that the regulation of neurotransmission is different in the striatonigral and striatopallidal GABA pathways.Neuronal plasticity is mediated by alterations in gene expression patterns. The first stage of this genomic reaction to environmental cues culminates in the selective short-term expression of transactivating proteins that influence the transcription of downstream genes involved in long-term changes in the cellular phenotype. This stimulus-transcription coupling in the brain is particularly well established for the c-fos gene and other members of the fos and jun gene families (1-3). Dopamine (DA) releasing drugs (indirect agonists) like amphetamine and cocaine but also high doses of the DA agonist apomorphine stimulate locomotion and induce c-fos in the medium sized spiny striatonigral ␥-aminobutyric acid (GABA) neurons (4-10). Suppression of striatal c-fos expression by antisense oligonucleotides has recently been demonstrated to attenuate the effects of DA agonists on motor function. We reported earlier that rats which received an unilateral c-fos antisense infusion in the neostriatum developed a strong ipsilateral turning behavior within 15-20 min after systemic amphetamine administration (11). Others have found similar inhibitory effects on DA agonist stimulated motor behavior after intrastriatal infusion of c-fos antisense oligonucleotides (12)(13)(14). While both the induction of c-fos expression in the neostriatum and the locomotor behavior are mediated by the DA D 1 receptors, no functional link between them has been established earlier and the mechanisms underlying the c-fos antisense-induced reduction in motor function is unclear. Since in the above-mentioned studies the behavioral consequences occurred very rapidly after the rats had been treated with the ps...

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Section: Discussionmentioning

confidence: 99%

Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal γ-aminobutyric acid transmission in the conscious rat

Sommer

Rimondini

O’Connor

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, it has been proposed that NT receptors on dopaminergic neurones can decrease the e⁄cacy of D2 autoreceptors to inhibit dopamine release (Fuxe et al, 1992;Li et al, 1995;Shi and Bunney, 1991;Tanganelli et al, 1989;von Euler et al, 1991;Werkman et al, 2000). To test this possibility, we evaluated whether NT(8^13) decreases the ability of the D2 receptor agonist quinpirole to cause presynaptic inhibition of action potential-evoked EPSCs in isolated dopaminergic neurones, a modulation that has been identi¢ed as being mediated at the level of the nerve terminals (Congar and Trudeau, 1999).…”

Section: Evidence For a Presynaptic Neuromodulatory Actionmentioning

confidence: 99%

Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones

et al. 2002

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AbstractöDopamine-containing neurones of the ventral tegmental area express neurotensin receptors which are involved in regulating cell ¢ring and dopamine release. Although indirect evidence suggests that some neurotensin receptors may be localised on the nerve terminals of dopaminergic neurones in the striatum and thus locally regulate dopamine release, a clear demonstration of such a mechanism is lacking and a number of indirect sites of action are possible. We have taken advantage of a simpli¢ed preparation in which cultured rat ventral tegmental area dopaminergic neurones establish nerve terminals that co-release glutamate to determine whether neurotensin can act at presynaptic sites. We recorded glutamatemediated synaptic currents that were generated by dopaminergic nerve terminals as an index of presynaptic function. The neurotensin receptor agonist NT(8^13) caused an inward current and an enhancement of the ¢ring rate of dopaminergic neurones together with an increase in the frequency of spontaneous glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). Incompatible with a direct excitatory action on nerve terminals, NT(8^13) failed to change the amplitude of individual action potential-evoked EPSCs or the frequency of miniature EPSCs recorded in the presence of tetrodotoxin. However, NT(8^13) reduced the ability of terminal D2 dopamine receptors to inhibit action potentialevoked EPSCs in isolated dopaminergic neurones. Taken together, our results suggest that in addition to its well-known somatodendritic excitatory e¡ect leading to an increase in ¢ring rate, neurotensin also acts on nerve terminals. The main e¡ect of neurotensin on nerve terminals is not to produce a direct excitation, but rather to decrease the e¡ectiveness of D2 receptor-mediated presynaptic inhibition. ß

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“…There exists substantial pharmacological evidence showing that NT is involved in the regulation of DA neurotransmission. For example, local perfusion with NT dose-dependently increases striatal extracellular DA levels without affecting DA metabolite levels and modifies the inhibitory effects of DA-D 1 and DA-D 2 receptor agonists on striatal DA release (Fuxe et al 1992). In contrast to the striatum, in the nucleus accumbens direct infu-N EUROPSYCHOPHARMACOLOGY 2002 -VOL .…”

mentioning

confidence: 99%

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Gruber

Nomikos

Mathé

2002

Neuropsychopharmacology

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Neurotensin (NT) may play a role in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs. Here we studied the effects of a 30-day regimen of haloperidol (1.15 mg/100 g food) and risperidone (1.15 and 2.3 mg/100 g food) on NT-like immunoreactivity (-LI) levels in brain tissue and NT-LI efflux in the ventral striatum (VSTR) of the rat. Haloperidol, but not risperidone, increased NT-LI levels in the striatum. In the occipital cortex, risperidone, but not haloperidol, decreased levels of NT-LI. In the hippocampus and the frontal cortex both haloperidol and risperidone (the higher dose) increased NT-LI levels. In the VSTR, haloperidol and risperidone (the higher dose) decreased NT-LI efflux and abolished the stimulatory effect of d-amphetamine (1.5 mg/kg, s.c.). Thus, changes in NT occur in response toNeurotensin (NT) is a 13-amino acid peptide originally isolated from hypothalamus (Carraway and Leeman 1973). Several anatomical, behavioral and pharmacological studies have demonstrated an interaction between NT and dopamine (DA) in the central nervous system (CNS). For example, high levels of NT and its binding sites have been found in both the cell body regions, i.e. the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA), as well as the major projection areas of the ascending dopaminergic pathways, i.e. the striatum and the nucleus accumbens (Kasckow and Nemeroff 1991;Lambert et al. 1995; Quirion 1983). Within both the VTA and the SN, NT immunoreactive fibers are found in close proximity to DA cell bodies (Hökfelt et al. 1984); within the VTA, NT is colocalized with DA (Hökfelt et al. 1984;Kalivas 1993), while in the striatal complex, the majority of the NT binding sites in rat are located on DA terminals (Cadet et al. 1991). There exists substantial pharmacological evidence showing that NT is involved in the regulation of DA neurotransmission. For example, local perfusion with NT dose-dependently increases striatal extracellular DA levels without affecting DA metabolite levels and modifies the inhibitory effects of DA-D 1 and DA-D 2 receptor agonists on striatal DA release (Fuxe et al. 1992). In contrast to the striatum, in the nucleus accumbens direct infu- NO . 5 sion of NT does not affect extracellular DA levels, but increases extracellular levels of the DA metabolite homovanillic acid (Chapman et al. 1992). Microinjection of NT into the VTA, produces a dose-dependent in vivo DA release in the nucleus accumbens and also causes a dose-dependent circling behavior (Steinberg et al. 1995). Moreover, blockade of NT receptors by the NT receptor antagonist SR 48692 decreases basal extracellular levels of DA and its metabolites in the nucleus accumbens, suggesting that NT modulates the mesolimbic DA system (Azzi et al. 1998). Neurotensin has also been shown to mimic the effects of neuroleptic drugs in behavioral models of antipsychotic drug action. Thus, centrally injected NT antagonizes psychostimulant-induced locomotor hyperactivity (Ervin et al. 1981;Joli...

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Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum.

Cited by 72 publications

References 34 publications

Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal γ-aminobutyric acid transmission in the conscious rat

Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal γ-aminobutyric acid transmission in the conscious rat

Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

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