Serotonin 5-HT2A but not 5-HT2C receptor antagonism reduces hyperlocomotor activity induced in dopamine-depleted rats by striatal administration of the D1 agonist SKF 82958.
While recent work has indicated that D1 receptor agonist-induced hyperlocomotion in DA-depleted rats is reduced by striatal 5-HT2 receptor antagonism, the 5-HT receptor(s) subtypes mediating these effects are not yet known. In the present study, we examined the influence(s) of striatal 5-HT2A and 5-HT2C receptors on locomotor behavior induced by D1 agonism in neonatal DA-depleted rats. On postnatal day 3, male Sprague-Dawley rats (n=68) were treated with either vehicle or 6-hydroxydopamine (6-OHDA; 60 microg) which produced >98% DA depletion. Sixty days later, all rats were fitted with bilateral striatal cannulae. A subset of control and 6-OHDA-lesioned rats (n=20) was tested for locomotor responses to striatal infusion of the D1 agonist SKF 82958 (0, 0.1, 1.0, 10 microg/side). The remaining rats (n=48) were tested for locomotor responses to intrastriatal SKF 82958 (2.0 microg/side) alone or in combination with the 5-HT2A- or 5-HT2C-preferring antagonists M100907 or RS102221 (0.1 or 1.0 microg/side), respectively. Intrastriatal SKF 82958 dose-dependently increased measures of motor activity within DA-depleted rats. This hyperlocomotor activity was suppressed by co-infusion of M100907, but not RS102221. These results indicate that DA depletion strengthens striatal 5-HT2A/D1 receptor interactions and suggest that 5-HT2A receptor antagonists may prove useful in reducing D1-related movements.
Department of Anatomy & Cell Biology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA.
Christopher
C
Bishop
Gregory S
GS
Daut
Paul D
PD
Walker
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004563:Electrochemistry; D005464:Fluorobenzenes / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D013565:Sympatholytics
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D001552:Benzazepines; D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; D013565:Sympatholytics; C071262:SK&F 82958; D016627:Oxidopamine; C079049:volinanserin; D004298:Dopamine