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Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice.
J Pharmacol Exp Ther. 2005 Feb; 312(2):733-41.JP

Abstract

D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and the D1-like agonist R-6-Br-APB [R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in Sprague-Dawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naptho-(2,1-b)azepine] (1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans.

Authors+Show Affiliations

Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. rralph@mclean.harvard.eduNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15494551

Citation

Ralph, Rebecca J., and S Barak Caine. "Dopamine D1 and D2 Agonist Effects On Prepulse Inhibition and Locomotion: Comparison of Sprague-Dawley Rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 2, 2005, pp. 733-41.
Ralph RJ, Caine SB. Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice. J Pharmacol Exp Ther. 2005;312(2):733-41.
Ralph, R. J., & Caine, S. B. (2005). Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice. The Journal of Pharmacology and Experimental Therapeutics, 312(2), 733-41.
Ralph RJ, Caine SB. Dopamine D1 and D2 Agonist Effects On Prepulse Inhibition and Locomotion: Comparison of Sprague-Dawley Rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J Mice. J Pharmacol Exp Ther. 2005;312(2):733-41. PubMed PMID: 15494551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice. AU - Ralph,Rebecca J, AU - Caine,S Barak, Y1 - 2004/10/19/ PY - 2004/10/21/pubmed PY - 2005/3/19/medline PY - 2004/10/21/entrez SP - 733 EP - 41 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 312 IS - 2 N2 - D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and the D1-like agonist R-6-Br-APB [R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in Sprague-Dawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naptho-(2,1-b)azepine] (1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15494551/Dopamine_D1_and_D2_agonist_effects_on_prepulse_inhibition_and_locomotion:_comparison_of_Sprague_Dawley_rats_to_Swiss_Webster_129X1/SvJ_C57BL/6J_and_DBA/2J_mice_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15494551 DB - PRIME DP - Unbound Medicine ER -