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The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat.
Brain Res. 2007 Jul 16; 1158:135-43.BR

Abstract

Serotonin 1A receptor (5-HT(1A)R) agonists have emerged as valuable supplements to l-DOPA therapy, demonstrating that they can decrease side effects and enhance motor function in animal models of Parkinson's disease (PD) and human PD patients. The precise mechanism by which these receptors act remains unknown and there is limited information on how 5-HT(1A)R stimulation impacts striatal dopamine (DA) D1 receptor (D1R) and D2 receptor (D2R) function. The current study examined the effects of 5-HT(1A)R stimulation on DA receptor-mediated behaviors. Male Sprague-Dawley rats were rendered hemiparkinsonian by unilateral 6-OHDA lesions and primed with the D1R agonist SKF81297 (0.8 mg/kg, i.p.) in order to sensitize DA receptors. Using a randomized within subjects design, rats received a first injection of: Vehicle (dH(2)O) or the 5-HT(1A)R agonist +/-8-OH-DPAT (0.1 or 1.0 mg/kg, i.p.), followed by a second injection of: Vehicle (dimethyl sulfoxide), the D1R agonist SKF81297 (0.8 mg/kg, i.p.), the D2R agonist quinpirole (0.2 mg/kg, i.p.), or l-DOPA (12 mg/kg+benserazide, 15 mg/kg, i.p.). On test days, rats were monitored over a 2-h period immediately following the second injection for abnormal involuntary movements (AIMs), analogous to dyskinesia observed in PD patients, and contralateral rotations. The present findings indicate that 5-HT(1A)R stimulation reduces AIMs induced by D1R, D2R and l-DOPA administration while its effects on DA agonist-induced rotations were receptor-dependent, suggesting that direct 5-HT(1A)R and DA receptor interactions may contribute to the unique profile of 5-HT(1A)R agonists for the improvement of PD treatment.

Authors+Show Affiliations

Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17553470

Citation

Dupre, Kristin B., et al. "The Differential Effects of 5-HT(1A) Receptor Stimulation On Dopamine Receptor-mediated Abnormal Involuntary Movements and Rotations in the Primed Hemiparkinsonian Rat." Brain Research, vol. 1158, 2007, pp. 135-43.
Dupre KB, Eskow KL, Negron G, et al. The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Res. 2007;1158:135-43.
Dupre, K. B., Eskow, K. L., Negron, G., & Bishop, C. (2007). The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Research, 1158, 135-43.
Dupre KB, et al. The Differential Effects of 5-HT(1A) Receptor Stimulation On Dopamine Receptor-mediated Abnormal Involuntary Movements and Rotations in the Primed Hemiparkinsonian Rat. Brain Res. 2007 Jul 16;1158:135-43. PubMed PMID: 17553470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. AU - Dupre,Kristin B, AU - Eskow,Karen L, AU - Negron,Giselle, AU - Bishop,Christopher, Y1 - 2007/05/08/ PY - 2007/03/28/received PY - 2007/04/27/revised PY - 2007/05/02/accepted PY - 2007/6/8/pubmed PY - 2007/10/13/medline PY - 2007/6/8/entrez SP - 135 EP - 43 JF - Brain research JO - Brain Res VL - 1158 N2 - Serotonin 1A receptor (5-HT(1A)R) agonists have emerged as valuable supplements to l-DOPA therapy, demonstrating that they can decrease side effects and enhance motor function in animal models of Parkinson's disease (PD) and human PD patients. The precise mechanism by which these receptors act remains unknown and there is limited information on how 5-HT(1A)R stimulation impacts striatal dopamine (DA) D1 receptor (D1R) and D2 receptor (D2R) function. The current study examined the effects of 5-HT(1A)R stimulation on DA receptor-mediated behaviors. Male Sprague-Dawley rats were rendered hemiparkinsonian by unilateral 6-OHDA lesions and primed with the D1R agonist SKF81297 (0.8 mg/kg, i.p.) in order to sensitize DA receptors. Using a randomized within subjects design, rats received a first injection of: Vehicle (dH(2)O) or the 5-HT(1A)R agonist +/-8-OH-DPAT (0.1 or 1.0 mg/kg, i.p.), followed by a second injection of: Vehicle (dimethyl sulfoxide), the D1R agonist SKF81297 (0.8 mg/kg, i.p.), the D2R agonist quinpirole (0.2 mg/kg, i.p.), or l-DOPA (12 mg/kg+benserazide, 15 mg/kg, i.p.). On test days, rats were monitored over a 2-h period immediately following the second injection for abnormal involuntary movements (AIMs), analogous to dyskinesia observed in PD patients, and contralateral rotations. The present findings indicate that 5-HT(1A)R stimulation reduces AIMs induced by D1R, D2R and l-DOPA administration while its effects on DA agonist-induced rotations were receptor-dependent, suggesting that direct 5-HT(1A)R and DA receptor interactions may contribute to the unique profile of 5-HT(1A)R agonists for the improvement of PD treatment. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17553470/The_differential_effects_of_5_HT_1A__receptor_stimulation_on_dopamine_receptor_mediated_abnormal_involuntary_movements_and_rotations_in_the_primed_hemiparkinsonian_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(07)01064-5 DB - PRIME DP - Unbound Medicine ER -