Effects of 7-hydroxy- N, N-di- n-propylaminotetralin on behaviour and blood pressure of spontaneously hypertensive rats

Abstract

The in vivo effects of administration of the putative dopamine D 3 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 D 2 receptors or non-dopaminergic receptors. Thus, more selective dopamine D 3 receptor agonists or -antagonists are needed to further explore the role of dopamine D 3 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.