Serotonin regulation of tachykinin biosynthesis in the rat neostriatum

Walker, Paul D.; Riley, Leigh A.; Hart, Ronald P.; Jonakait, G. Miller

doi:10.1016/0006-8993(91)91155-t

Cited by 53 publications

(22 citation statements)

References 56 publications

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“…29,30 In agreement with a previous observation, 37 we found that amitriptyline and fluoxetine increased substance P mRNA in the shell of nucleus accumbens, which might be the result of an increased D 3 receptor function. Since antidepressant treatments decrease substance P concentrations, 38 they may accelerate substance P turnover and release.…”

Section: Molecular Psychiatrysupporting

confidence: 92%

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

Díaz

et al. 2000

Mol Psychiatry

137

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The mesolimbic dopaminergic system is a neuroanatomical key structure for reward and motivation upon which previous studies indicated that antidepressant drugs exert a stimulatory influence, via still unknown neurobiological mechanisms. Here we examined the effects of chronic administration of antidepressants of several classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine) and repeated electroconvulsive shock treatments (ECT) on dopamine D 3 receptor expression in the shell of the nucleus accumbens, a major projection area of the mesolimbic dopaminergic system. Short-term drug treatments had variable effects on D

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Section: Molecular Psychiatrysupporting

confidence: 92%

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

Díaz

et al. 2000

Mol Psychiatry

137

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“…Quinpirole might also induce PPT mRNA directly by stimulation of D3 receptors that are known to be de novo expressed by striatonigral neurons in dopamine-depleted striatum after priming with directly acting dopaminergic agonists (Bordet et al, 2000). Dopamine or serotonin depletion downregulates striatal PPT mRNA (Walker et al, 1991). It seems that on the dopaminergically intact side, the D2 antagonistic effects of LEK-8829 on PPT mRNA expression prevailed over its D1 agonistic effects, whereas on the dopamine-depleted side, D1 agonistic effects prevailed over D2 antagonistic effects.…”

Section: D1 Intrinsic Activity Of Lek-8829 365mentioning

confidence: 99%

Modulation of Neuroleptic Activity of 9,10-Didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline Bimaleinate (LEK-8829) by D1 Intrinsic Activity in Hemi-Parkinsonian Rats

2002

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Parkinsonism, a common unwanted side effect of typical antipsychotic (neuroleptic) drugs, is induced by the blockade of striatal dopamine D2 receptors. In rats with hemi-parkinsonism induced by unilateral lesion of dopaminergic nigrostriatal neurons with 6-hydroxydopamine, D2 antagonists inhibit contralateral turning induced by D2 agonists and augment the levels of neurotensin mRNA in dopaminergically intact striatum. By contrast, D1 agonists induce contralateral turning and augment neurotensin mRNA levels in dopamine-depleted striatum. These effects could be inhibited by D1 but not by D2 antagonists. Here we used a hemi-parkinsonian model to investigate the effects of putative D1 agonist/D2 antagonist LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate), an experimental antipsychotic, on turning behavior and the expression of striatal neurotensin, preprotachykinin and neurotransmitter-induced early gene protein 4 (ania-4) mRNAs. We found that LEK-8829 inhibited contralateral turning induced by D2 agonist quinpirole, but only if the rats were cotreated with D1 antagonist SCH-23390. In situ hybridization showed that LEK-8829 induced the expression of neurotensin and ania-4 mRNAs in dopamine-intact striatum that could be completely blocked only by the combined treatment with SCH-23390 and quinpirole. In addition, LEK-8829 augmented the expression of neurotensin, preprotachykinin and ania-4 mRNAs in dopamine-depleted striatum that could be completely blocked by SCH-23390. This study clearly demonstrates that in hemi-parkinsonian rats D1 agonistic activity of LEK-8829 confers its anti-parkinsonian drug-like properties and modulates its neuroleptic drug-like properties, which are dependent on the blockade of dopamine D2 receptors. These findings imply that atypical antipsychotics with D1 intrinsic activity might have a reduced propensity for the induction of extrapyramidal syndrome.The blockade of dopamine D2 receptors by typical antipsychotics (neuroleptics) often provokes unwanted extrapyramidal syndrome (EPS), characterized by parkinsonism, akathisia, catalepsy, and, after long-term treatment, tardive dyskinesia (Deniker, 1990). Fortunately, atypical antipsychotic drugs, such as clozapine, were developed that have a lower tendency for the induction of EPS. Atypical antipsychotics are characterized by high-affinity ratio between serotonin 5-HT2 and dopamine D2 receptors (Meltzer et al., 1989). Their low propensity for the induction of EPS is thought to depend on their ability to preferentially inhibit mesolimbic dopaminergic system as opposed to neuroleptic drugs that effectively inhibit both mesolimbic and mesostriatal dopaminergic systems (Scatton and Sanger, 2000).The receptor binding profile of 9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate (LEK-8829) was determined in vitro by displacement of appropriate radioligands in preparations of rat brain membranes and of cells expressing recombinant subtypes of human dopamine and serotonin r...

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“…Although our results suggest that 5-HT removal pro vides a positive regulatory influence on striatal tachy kinin biosynthesis, studies in the adult rat suggest that continuous 5-HT depletion by /7-chlorophenylalanine may ultimately down-regulate PPT mRNA synthesis within the striatum [22], These results are supported by recent findings [44] that direct 5,7-DHT injections of the adult striatum and that the subchronic reduction of 5-HT release by daily intraperitoneal injections of the 5-HT,A receptor agonist 8-OH-DPAT both reduce striatal PPT mRNA levels. In contrast, stimulation of 5-HT neuro transmission by uptake inhibition [22,23] or 5-HT, receptor activation [22,44] up-regulates striatal PPT mRNA levels.…”

Section: Discussionmentioning

confidence: 61%

“…Total RNA was extracted from striatal samples using the acid guanidinium thiocyanate-phenol-chlorofomi procedure of Chomczynski and Sacchi [25] as described previously [12,15,22). These samples were prepared and stored separately for each individual ani mal.…”

Section: Northern Analysismentioning

confidence: 99%

“…This pattern of neuropeptide biosynthetic maturation may be related to intense synaptogenesis within the striatum during this same period [16], a phenomenon! likely regulated by striatal afferents including serotonin fibers from mid brain raphe nuclei [17][18][19][20], In the adult striatum, tachykinin mRNA and peptide biosynlheses are known to be sensitive to changes in serotonin neurotransmission [21][22][23]. Within the developing striatum, 5-HT may also trans-synaptically influence the pattern of striatal tachy kinin maturation and possibly the entire connective orga nization of the basal ganglia and forebrain.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in the Postnatal Development of Striatal Preprotachykinin but Not Preproenkephalin mRNA Expression in the Serotonin-Depleted Rat

Walker

Wolf

1997

Dev Neurosci

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We examined the effects of diminished serotonin (5-hydroxytryptamine, 5-HT) levels on the postnatal development of striatal tachykinin and enkephalin neuropeptide systems. Neonatal rats received intracisternal injection of vehicle or the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 100 pg) on postnatal day 2 followed by sacrifice 1–29 days later. Monoamine analysis by high-performance liquid chromatography with electrochemical detection revealed a drastic reduction of midbrain 5-HT levels, but not norepinephrine or dopamine, as early as 1 day and extending to 29 days following 5,7-DHT injection. Striatal preprotachykinin (PPT) mRNA levels were significantly increased 8 days following injection. However, PPT mRNA amounts failed to remain up-regulated, falling back to or below control levels during the second and third weeks following injection. By day 29, striatal PPT mRNA had normalized to control levels even though 5-HT amounts were still markedly reduced. Throughout the entire time course, striatal preproenkephalin mRNA levels did not significantly differ from control levels. These results suggest that striatal tachykinin, but not enkephalin, neurons may be transiently sensitive to lowered 5-HT neurotransmission during postnatal development.

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Serotonin regulation of tachykinin biosynthesis in the rat neostriatum

Cited by 53 publications

References 56 publications

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

Modulation of Neuroleptic Activity of 9,10-Didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline Bimaleinate (LEK-8829) by D1 Intrinsic Activity in Hemi-Parkinsonian Rats

Alterations in the Postnatal Development of Striatal Preprotachykinin but Not Preproenkephalin mRNA Expression in the Serotonin-Depleted Rat

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