8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN INCREASES THE ACTIVITY OF ADENYLATE-CYCLASE IN THE HIPPOCAMPUS OF FREELY-MOVING RATS

The present study was designed to examine the effects of intraperitoneal (i.p.) administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid of the dorsal hippocampus, using in vivo microdialysis. One week after implantation of the guide, probes were inserted in conscious rats and perfused with Ringer solution. Steady basal levels of cAMP (2.9 +/- 0.1 pmol/ml, n = 74 rats) were obtained after at least three hours of stabilisation. The 8-OH-DPAT dose-dependently increased the basal efflux of cAMP, which was most apparent between 20-40 min after the injection. The largest dose of 8-OH-DPAT (1 mg/kg) tested, induced a maximum response of approximately 50%, whereas injections of saline did not alter the efflux of cAMP. Treatment with (+/-)pindolol (10 mg/kg) did not significantly affect the basal efflux of cAMP, whereas it markedly inhibited the increase in levels of cAMP, induced by 0.5 mg/kg 8-OH-DPAT (injected 40 min later). Simultaneous behavioural observations demonstrated that (+/-)pindolol also attenuated various components of the 8-OH-DPAT-induced behavioural syndrome. Addition of 3-isobutyl-1-methylxanthine (IBMX), forskolin or noradrenaline, to the perfusion fluid, strongly enhanced the levels of cAMP in the extracellular fluid from the hippocamus. Injection of 8-OH-DPAT (1 mg/kg) during perfusion with IBMX induced a similar increase in levels of cAMP, as under normal perfusion conditions. However, 8-OH-DPAT did not significantly alter the efflux of cAMP, when probes were perfused with either forskolin or forskolin and IBMX. The results suggest that 8-OH-DPAT modulates the activity of adenylate cyclase in the hippocampus of freely-moving rats through a 5-HT1A receptor mechanism.