Enhancement by a single dose of reserpine (plus alpha methyl-p-tyrosine) of the central stimulatory effects evoked by dopamine D-1 and D-2 agonists in the mouse.
With the advent of selective dopamine D-1 and D-2 agonists such as SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl) and quinpirole (LY171555, trans-4,4a,5,6,7,8a,9-octahydro-5-propyl-2H-pyrazolo [3,4-g]quinoline), it has become possible to examine the functional role of the two dopamine receptor subtypes as well as their interrelationship. In the present study, we pretreated mice with the granule-depleting agent reserpine (5 mg/kg sc) and tested the mice from 4 h to 10 days later. In all the studies, each mouse also received an injection of the dopamine synthesis inhibitor alpha methyl-p-tyrosine (200 mg/kg ip) 1 h before agonist challenge. Where the reserpine was given 2 or more days before testing, a second dose of reserpine was given 4 h before agonist challenge. While producing no significant locomotor stimulation 4 h after reserpine, SKF38393 produced a dose-dependent increase in coordinated locomotion 24 h and 3 days after the reserpine. Likewise, quinpirole itself produced no significant alteration in activity at 4 h, but significantly increased activity at 24 h and 3 days. The new selective D-1 agonist CY208-243 ((-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo [4,3-ab] phenanthridine), unlike SKF38393, produced some increase in activity 4 h after reserpine, but much greater activity was seen 1 and 3 days after reserpine. The enhancement with SKF38393, CY208-243 and quinpirole was most marked 3 days after the reserpine. The behavioural stimulation produced by the mixed D1/D2 agonist apomorphine was also greater 3 days after reserpine pretreatment than after 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Ross
S B
SB
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Jackson
D M
DM
Wallis
E M
EM
Edwards
S R
SR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D007211:Indoles; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010617:Phenanthridines; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects; D019805:alpha-Methyltyrosine
D001067:Appetite Depressants; D001552:Benzazepines; D004873:Ergolines; D007211:Indoles; D008781:Methyltyrosines; D010617:Phenanthridines; D011954:Receptors, Dopamine; C054531:CY 208-243; D019257:Quinpirole; D019805:alpha-Methyltyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012110:Reserpine