PARAVENTRICULAR NUCLEUS INJECTIONS OF IDAZOXAN BLOCK FEEDING INDUCED BY PARAVENTRICULAR NUCLEUS NOREPINEPHRINE BUT NOT INTRA-RAPHE 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN

Previous work has shown that injection of the 5-hydroxytryptamine (5-H T)1A agonist -hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into th e midbrain raphe nuclei activates somatodendritic 5-HT autoreceptors l eading to decreased 5-HT synthesis and release in terminal forebrain r egions and an increase in feeding behaviour. Since 5-HT is believed to function antagonistically with norepinephrine (NE) in the hypothalami c paraventricular nucleus (PVN) to control feeding, it has been propos ed that 8-OH-DPAT elicits food intake by removing the inhibitory influ ence of 5-HT over PVN a2-adrenergic feeding mechanisms. This hypothesi s was tested by examining the ability of PVN injection of the alpha2-a drenoceptor antagonist idazoxan (IDAZ) to attenuate the feeding stimul ant action induced by raphe injection of 8-OH-DPAT. In the first serie s of experiments the dose-response effects of dorsal and median raphe injection of 8-OH-DPAT in addition to PVN NE on feeding were examined. Injection of NE (5-40 nmol) and 8-OH-DPAT (0.4-1.6 nmol) both elicite d reliable dose-dependent increases in 1 h food intake compared to sal ine control. Similar doses of 8-OH-DPAT injected into the PVN failed t o alter baseline feeding. A second series of experiments examined the effects of IDAZ on 8-OH-DPAT and NE-stimulated food intake in rats imp lanted with dorsal or median raphe cannulae as well as cannulae aimed at the PVN. Although PVN injection of IDAZ (12.5-50 nmol) effectively attenuated PVN NE (20 nmol) feeding, it did not affect feeding resulti ng from dorsal raphe or median raphe injection of 8-OH-DPAT (0.8 nmol) . The inability of IDAZ to IDAZ to block 8-OH-DPAT-induced food intake suggests that feeding elicited by this 5-HT1A agonist is not mediated by PVN alpha2-adrenergic systems.