Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion
To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg...
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ndltd-ETSU-oai-dc.etsu.edu-etd-40772019-05-16T04:51:27Z Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion Gong, Li To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change in the percentage of high affinity D$\sb1$ sites in these groups of rats. Striatal mRNA levels for D$\sb1$ receptors were reduced in the lesioned rats, but restored to control level after treatments with SKF 38393 in adulthood. Basal, DA-, NaF- and forskolin-stimulated adenylate cyclase activities were similar among treatment groups. Striatal DA content was reduced ($>$99%), whereas serotonin (5-HT) content was elevated ($>$50%) in the 6-OHDA groups. To study possible interaction between DA and 5-HT systems, the effects of a series of 5-HT agents on the induction of oral activity were determined. The 5-HT$\sb{\rm 1C}$ receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a marked increase in oral activity in 6-OHDA-lesioned rats. The respective 5-HT$\sb{\rm 1A}$ and 5-HT$\sb{\rm 1B}$ agonists, 8-OH-DPAT and CGS-12066B did not increase oral activity. The m-CPP-induced oral response in the lesioned rats was attenuated by mianserin, a 5-HT$\sb{\rm 1C}$ antagonist, but not by ketanserin or MDL-72222, 5-HT$\sb2$ and 5-HT$\sb3$ antagonists, respectively. Although the supersensitized oral response of lesioned rats to m-CPP was not attenuated by SCH 23390, the enhanced response of SKF 38393 was attenuated by mianserin. Additionally, mRNA levels for 5-HT$\sb{\rm 1C}$ receptor were not altered in both intact and lesioned rats. These findings demonstrate that ontogenetic treatments of neonatal 6-OHDA-lesioned rats with a D$\sb1$ agonist produce partial sensitization of DA D$\sb1$ receptors in adulthood without altered biochemical markers, and that this neonatal lesion is associated with both supersensitized DA D$\sb1$ and 5-HT$\sb{\rm 1C}$ receptors. Moreover, induction of oral activity by DA agonists is mediated via a serotonergic system. 1993-12-01T08:00:00Z text application/pdf https://dc.etsu.edu/etd/2686 https://dc.etsu.edu/cgi/viewcontent.cgi?article=4077&context=etd Electronic Theses and Dissertations Digital Commons @ East Tennessee State University Biological sciences Health and environmental sciences Neurology OHDA lesion Pharmacology Neurology Pharmacology |
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Biological sciences Health and environmental sciences Neurology OHDA lesion Pharmacology Neurology Pharmacology Gong, Li Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
description |
To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change in the percentage of high affinity D$\sb1$ sites in these groups of rats. Striatal mRNA levels for D$\sb1$ receptors were reduced in the lesioned rats, but restored to control level after treatments with SKF 38393 in adulthood. Basal, DA-, NaF- and forskolin-stimulated adenylate cyclase activities were similar among treatment groups. Striatal DA content was reduced ($>$99%), whereas serotonin (5-HT) content was elevated ($>$50%) in the 6-OHDA groups. To study possible interaction between DA and 5-HT systems, the effects of a series of 5-HT agents on the induction of oral activity were determined. The 5-HT$\sb{\rm 1C}$ receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a marked increase in oral activity in 6-OHDA-lesioned rats. The respective 5-HT$\sb{\rm 1A}$ and 5-HT$\sb{\rm 1B}$ agonists, 8-OH-DPAT and CGS-12066B did not increase oral activity. The m-CPP-induced oral response in the lesioned rats was attenuated by mianserin, a 5-HT$\sb{\rm 1C}$ antagonist, but not by ketanserin or MDL-72222, 5-HT$\sb2$ and 5-HT$\sb3$ antagonists, respectively. Although the supersensitized oral response of lesioned rats to m-CPP was not attenuated by SCH 23390, the enhanced response of SKF 38393 was attenuated by mianserin. Additionally, mRNA levels for 5-HT$\sb{\rm 1C}$ receptor were not altered in both intact and lesioned rats. These findings demonstrate that ontogenetic treatments of neonatal 6-OHDA-lesioned rats with a D$\sb1$ agonist produce partial sensitization of DA D$\sb1$ receptors in adulthood without altered biochemical markers, and that this neonatal lesion is associated with both supersensitized DA D$\sb1$ and 5-HT$\sb{\rm 1C}$ receptors. Moreover, induction of oral activity by DA agonists is mediated via a serotonergic system. |
author |
Gong, Li |
author_facet |
Gong, Li |
author_sort |
Gong, Li |
title |
Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
title_short |
Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
title_full |
Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
title_fullStr |
Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
title_full_unstemmed |
Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion |
title_sort |
co-sensitization of dopamine and serotonin receptors occurs in the absence of a change in the dopamine d1 receptor complex after a neonatal 6-ohda lesion |
publisher |
Digital Commons @ East Tennessee State University |
publishDate |
1993 |
url |
https://dc.etsu.edu/etd/2686 https://dc.etsu.edu/cgi/viewcontent.cgi?article=4077&context=etd |
work_keys_str_mv |
AT gongli cosensitizationofdopamineandserotoninreceptorsoccursintheabsenceofachangeinthedopamined1receptorcomplexafteraneonatal6ohdalesion |
_version_ |
1719188484840751104 |