Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 2582610

Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat.

M R Pranzatelli·Y Y Huang·A M Dollison·M Stanley
View original source ↗Export metadata ↓

Abstract

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.

Explore related subjects

5,7-Dihydroxytryptamine5-HydroxytryptophanAnimalsAnimals, NewbornBehavior, AnimalBrain StemDihydroxytryptaminesRatsRats, Inbred StrainsSerotoninTime FactorsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M R Pranzatelli, Y Y Huang, A M Dollison, M Stanley. 1989-11-01. Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat.. https://doi.org/10.1016/0165-3806(89)90128-4

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Mechanisms underlying the long-term behavioral effects of traumatic experience in rats: the role of serotonin/noradrenaline balance and NMDA receptors.

Traumatic stressors induce long-lasting changes in behavior. It is believed that all three glutamatergic, serotonergic and noradrenergic neurotransmission play a role in the development of such behavioral changes, but their relative importance and relationship is poorly understood. We have shown previously that a single exposure of rats to electric shocks induces social avoidance for about 10 days. Here we assessed social avoidance 24 h after shock exposure in rats with chemically lesioned serotonergic and noradrenergic neurons. The effects of the NMDA receptor blocker MK-801 were also studied. When the serotonin/noradrenaline balance was shifted towards serotonergic dominance via chemical lesions, the behavioral dysfunction was markedly attenuated. The disruption of serotonergic neurotransmission (that lead to noradrenergic dominance) significantly increased the behavioral deficit. Shock responding was not secondary to lesion-induced differences in social behavior. Noteworthy, the brain noradrenaline/serotonin ratio correlated negatively with shock-induced social avoidance, suggesting that the ratio rather than absolute levels are important in this respect. In line with this assumption, double lesions had minor effects on social avoidance, suggesting that these monoaminergic systems modulate, but do not mediate the behavioral deficit. The blockade of NMDA receptors abolished the development of stress-induced social avoidance both when applied before shocks and when applied before behavioral testing. We confirmed that the long-term behavioral effects of traumatic experience result from glutamatergic activation, the effects of which are mediated by NMDA receptors. The development of the behavioral deficit is modulated by the balance between serotonergic and noradrenergic neurotransmission, possibly via effects on shock-induced glutamatergic activation.

5,7-Dihydroxytryptamine↗
PubMed2006

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain.

The present study quantified the cleaved form of the microtubule-associated protein tau (cleaved MAP-tau, C-tau), a previously demonstrated marker of CNS toxicity, following the administration of monoamine-depleting regimens of the psychostimulant drugs amphetamine (AMPH), methamphetamine (METH), +/-3,4-methylenedioxymethamphetamine (MDMA), or para-methoxyamphetamine (PMA) in an attempt to further characterize psychostimulant-induced toxicity. A dopamine (DA)-depleting regimen of AMPH produced an increase in C-tau immunoreactivity in the striatum, while a DA- and serotonin (5-HT)-depleting regimen of METH produced an increase in the number of C-tau immunoreactive cells in the striatum and CA2/CA3 and dentate gyrus regions of the hippocampus. MDMA and PMA, two psychostimulant drugs that produce selective 5-HT depletion in the striatum, had no effect on C-tau immunoreactivity in the striatum or hippocampus. Furthermore, 5,7-dihydroxytryptamine (5,7-DHT), an established 5-HT selective neurotoxin, did not produce an increase in C-tau immunoreactivity. Dual fluorescent immunocytochemistry with antibodies to glial fibrillary acidic protein (GFAP) and C-tau indicated that C-tau immunoreactivity was present in astrocytes, not neurons, suggesting that increased C-tau may be an alternative indicator of reactive gliosis. The present results are consistent with previous findings that the DA-depleting psychostimulants AMPH and METH produce reactive gliosis whereas the 5-HT-depleting drugs MDMA and PMA, as well as the known 5-HT selective neurotoxin 5,7-DHT, do not produce an appreciable glial response.

5,7-Dihydroxytryptamine↗
PubMed2006

Striatal serotonin depletion facilitates rat egocentric learning via dopamine modulation.

Egocentric spatial learning has been defined as the ability to navigate in an environment using only proprioceptive information, thereby performing a motor response based on one's own movement. This form of learning has been associated with the neural memory system, including the striatum body. Cerebral serotonin depletion induces better performance, both in tasks with strong egocentric components and in egocentric navigation in the Morris' maze. Based on this, we propose that the striatal serotonergic depletion must facilitate egocentric learning. Fifteen female Sprague Dawley rats weighing 250-350 g and maintained under standard conditions were chronically implanted with infusion cannulas for bilateral application of drugs into the striatum. The animals were evaluated for egocentric navigation using the Morris' maze, under different conditions: saline solution infusion, serotonin depletion by infusion of 5,7-Dihydroxytryptamine (25 microg of free base solved in 2.5 microl of ascorbic acid 1% in saline solution), infusion of mixed dopamine D(1) and D(2) receptor antagonists (0.5 microl/min during 5 min of mixed spiperone 20 microM and SCH23390 10 microM), or serotonin depletion and dopamine blockade simultaneously. Striatal serotonin depletion facilitated egocentric learning, which was demonstrated as shorter escape latencies and the display of a defined sequence of movements for reaching the platform. The facilitation was not observed under condition of simultaneous dopamine blockade. Striatal serotonin depletion produced a dopamine-dependent facilitation of egocentric learning. A role for serotonin in the inhibition of striatal-mediated learning strategies is proposed.

5,7-Dihydroxytryptamine↗