EFFECTS OF 7-HYDROXY-N,N-DI-N-PROPYLAMINOTETRALIN ON BEHAVIOR 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. The results furthermore support the concept that SHR display differential changes in central dopaminergic function, which could play a role in the development of hypertension.