Effects of 7-hydroxy-N,N-di-n-propylaminotetralin on behaviour and blood pressure of spontaneously hypertensive rats.
The in vivo effects of administration of the putative dopamine D3 receptor agonist 7-hydroxy-N,N-di-n-propylaminotetralin (7-OH-DPAT) were investigated in spontaneously hypertensive rats (SHR) and normotensive wistar-Kyoto controls (WKY). The i.p. injection of 7-OH-DPAT induced hyperactivity in WKY at 10 mg/kg, but only an inhibition of exploratory locomotor activity was observed in SHR at 1 mg/kg. In WKY and SHR with unilateral lesions of the nigrostriatal system, s.c. injection of 0.01-1 mg/kg of 7-OH-DPAT induced dose-dependent contralateral turning behaviour. This response was more pronounced in SHR than in WKY. The s.c. injection of 0.03, but not of 0.01 or 0.1 mg/kg, of 7-OH-DPAT induced yawning in WKY and SHR. The i.v. injection of 0.1 or 1 mg/kg of 7-OH-DPAT induced an immediate rise in blood pressure in both WKY and SHR. Pretreatment with the dopamine receptor antagonist haloperidol partially prevented this pressor response and, in addition, unmasked a late fall in blood pressure in SHR. The s.c. injection of 1 mg/kg of 7-OH-DPAT induced a decrease in body temperature, which was more pronounced in SHR than in WKY. This effect could be inhibited by pretreatment with haloperidol, but a residual hypothermia remained in SHR. These results suggest that 7-OH-DPAT induces a variety of effects in vivo, many of which may be mediated by dopamine D2 receptors or non-dopaminergic receptors. Thus, more selective dopamine D3 receptor agonists or -antagonists are needed to further explore the role of dopamine D3 receptors in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Van den Buuse
M
M
Marion Merrell Dow Research Institute, Strasbourg, France.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects
C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D003891:Desipramine; D004298:Dopamine