Involvement of 5‐HT1A‐ and α2‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin

1 Intracellular recordings were made from neurones of the submucous plexus and from submucosal arteriolar smooth muscle of the guinea-pig ileum for the purpose of examining the actions of 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT).2 8-OH-DPAT (10 nM-20 gM) had no direct presynaptic or postsynaptic actions on submucous plexus neurones. 3 Membrane hyperpolarizations induced in neurones by noradrenaline or UK 14304 were competitively antagonized by 8-OH-DPAT. For dose-ratios up to 40, Schild plots were linear with slopes not significantly different from unity; pA2 values for the 8-OH-DPAT antagonism of postsynaptic M2-adrenoceptors were 6.9-7.2. 4 The inhibitory synaptic potential, which is due to activation of cz2-adrenoceptors located on submucous plexus neurones, was selectively inhibited by 8-OH-DPAT; the IC5, value for inhibition of the inhibitory synaptic potential was 250 nM. 5 Neuronal hyperpolarizations mediated through activation of 6-opioid receptors or somatostatin receptors were unaffected by 8-OH-DPAT (0.1-1 I-M). 6 The ability of noradrenaline and UK 14304 to inhibit the release of acetylcholine at synapses in the submucous plexus, and to inhibit the release of the transmitter which mediates the excitatory junction potential in the submucosal arteriolar smooth muscle, was also blocked by 8-OH-DPAT. 7 These results suggest that some of the actions of 8-OH-DPAT previously ascribed to agonism at 5-hydroxytryptamine (5-HT), receptors may actually result from blockade of the actions of endogenously released noradrenaline acting on M2-adrenoceptors.

Section: Discussionmentioning

confidence: 36%

Evidence that 8‐hydroxy‐2‐(n‐dipropylamino)tetralin (8‐OH‐DPAT) is a selective α₂‐adrenoceptor antagonist on guinea‐pig submucous neurones

Crist

Surprenant

1987

“…Stimulation of 5-HTlA receptors has also been shown to increase food intake in rats (Dourish et al, 1985). In addition, idazoxan potentiates some of the behavioural effects of 5-HT agonists (Heal et al, 1986;Dickinson et al, 1991) although others, using different test systems, have shown antagonism (Fozard & McDermott, 1985;Marsden & Martin, 1986). It is unlikely that idazoxan interacts directly with 5-HT receptors since in vitro studies have shown that the concentration of idazoxan required to displace [3H]-5-HT from its binding sites in rat cerebral cortex is greater than 5 pM (A.C. Lane; personal communication).…”

Section: Discussionmentioning

confidence: 99%

The effects of idazoxan and other α₂‐adrenoceptor antagonists on food and water intake in the rat

Jackson

Griffin

Nutt

1991

1 Idazoxan (1, 3, l0mgkg-', i.p.) produced a significant increase in food and water intake in freely feeding rats during the daylight phase. 2 The more selective and specific a2-adrenoceptor antagonists, RX811059 (0.3, 1, 3 mgkg 1, i.p.) and RX821002 (0.3, 1, 3mg kg 1, i.p.), did not produce hyperphagia in rats, however, the highest dose produced a significant increase in water intake. 3 The peripherally acting a2-adrenoceptor antagonist, L-659,066 (1, 3, 10mgkg-1, i.p.), did not affect food intake in the 4h following injection, but the highest dose (l0mgkg '), produced a large increase in water intake. 4 These results indicate that a2-adrenoceptor antagonists may increase water intake by a peripherally mediated mechanism. 5 The lack of effect of RX811059 and RX821002 on food intake contrasts with the large dose-related increases induced by idazoxan and suggests that the hyperphagic effects of idazoxan are not due to a2-adrenoceptor blockade but may instead reflect its affinity for a non-adrenoceptor site, a property not shared by the other a2-antagonists.

“…The partial blockade by 8-OH-DPAT may reflect the use of a modest dose. Thus, it has previously been demonstrated that idazoxan completely blocked the effects of 8-OH-DPAT in moderating 5-HT release and metabolism in the suprachiasmatic nucleus (SCN) of the chloral hydrate anaesthetized rat (Marsden & Martin, 1986).…”

Section: Discussionmentioning

confidence: 99%

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

Cheng

Costall

Jin

et al. 1993

1 The interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5-hydroxytryptamine (5-HT) release in the frontal cortex of the freely-moving rat was assessed using the microdialysis technique.2 The a2-adrenoceptor antagonist, yohimbine (5.0 mg kg-', i.p.) increased maximally the extracellular levels of 5-HT in the rat frontal cortex by approximately 230% of the basal levels. failed to modify the response to yohimbine. 6 The present study provides evidence of the ability of the anxiogenic agent, yohimbine, to increase the activity of the central 5-hydroxytryptaminergic system and the ability of clonidine and various anxiolytic and putative anxiolytic agents to prevent the yohimbine response.