Recent evidence from our laboratory has demonstrated that blockade of somatodendritic 5-hydroxytryptamine (5-HT)(1A) au toreceptors by systemic administration of spiperone increases the firing rate of central serotonergic neurons in awake cats. The present study examines the effects of three other putative 5-HT1A antagonists (BMY 7378 {8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7, 9-dione}, NAN 190 {1-(2-methoxyphenyl)-4-[4-(2-phthali mido)butyl]piperazine} and (-)-propranolol) on the single-unit activity of serotonergic neurons recorded in the dorsal raphe nucleus of free-moving cats. Systemic administration of the phenylpiperazine derivatives BMY 7378 (5-100 mu g/kg i.v.) and NAN 190 (5-250 mu g/kg i.v.) produced a rapid, dose-dependent inhibition of neuronal activity with BMY 7378 being approximately twice as potent as NAN 190 (ED(50) = 15.3 mu g/kg vs. 34.2 mu g/kg). The suppression of neuronal activity produced by both compounds was greatly attenuated by spiperone(1 mg/kg i.v.). Systemic administration of (-)-propranolol (2 and 4 mg/kg i.v.) produced a modest suppression of serotonergic neuronal activity which did not appear to be dose-related. The ability of BMY 7378, NAN 190 and (-)-propranolol to block the suppression of neuronal activity produced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5HT(1A) agonist, was also examined. Pretreatment with these compounds had no significant effect on the inhibitory response of serotonergic neurons to and OH-DPAT challenge. These results indicate that BMY 7378 and NAN 190 act as agonists rather than antagonists at the somatodendritic 5-HT1A autoreceptor. Furthermore, (-)-propranolol, unlike spiperone, does not appear to be an effective 5-HT1A autoreceptor antagonist, because it did not block the action of 8-OH-DPAT or increase basal serotonergic neuronal activity in awake animals.

EFFECTS OF THE PUTATIVE 5-HYDROXYTRYPTAMINE(1A) ANTAGONISTS BMY-7378, NAN-190 AND (-)-PROPRANOLOL ON SEROTONERGIC DORSAL RAPHE UNIT-ACTIVITY IN BEHAVING CATS

MARROSU, FRANCESCO;
1994-01-01

Abstract

Recent evidence from our laboratory has demonstrated that blockade of somatodendritic 5-hydroxytryptamine (5-HT)(1A) au toreceptors by systemic administration of spiperone increases the firing rate of central serotonergic neurons in awake cats. The present study examines the effects of three other putative 5-HT1A antagonists (BMY 7378 {8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7, 9-dione}, NAN 190 {1-(2-methoxyphenyl)-4-[4-(2-phthali mido)butyl]piperazine} and (-)-propranolol) on the single-unit activity of serotonergic neurons recorded in the dorsal raphe nucleus of free-moving cats. Systemic administration of the phenylpiperazine derivatives BMY 7378 (5-100 mu g/kg i.v.) and NAN 190 (5-250 mu g/kg i.v.) produced a rapid, dose-dependent inhibition of neuronal activity with BMY 7378 being approximately twice as potent as NAN 190 (ED(50) = 15.3 mu g/kg vs. 34.2 mu g/kg). The suppression of neuronal activity produced by both compounds was greatly attenuated by spiperone(1 mg/kg i.v.). Systemic administration of (-)-propranolol (2 and 4 mg/kg i.v.) produced a modest suppression of serotonergic neuronal activity which did not appear to be dose-related. The ability of BMY 7378, NAN 190 and (-)-propranolol to block the suppression of neuronal activity produced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5HT(1A) agonist, was also examined. Pretreatment with these compounds had no significant effect on the inhibitory response of serotonergic neurons to and OH-DPAT challenge. These results indicate that BMY 7378 and NAN 190 act as agonists rather than antagonists at the somatodendritic 5-HT1A autoreceptor. Furthermore, (-)-propranolol, unlike spiperone, does not appear to be an effective 5-HT1A autoreceptor antagonist, because it did not block the action of 8-OH-DPAT or increase basal serotonergic neuronal activity in awake animals.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/38682
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 35
social impact