PMID- 9375958
OWN - NLM
STAT- MEDLINE
DCOM- 19980102
LR  - 20161019
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 122
IP  - 4
DP  - 1997 Oct
TI  - Enhancement and depression of spinal reflexes by 
      8-hydroxy-2-(di-n-propylamino)tetralin in the decerebrated and spinalized rabbit: 
      involvement of 5-HT1A- and non-5-HT1A-receptors.
PG  - 631-8
AB  - 1. In decerebrated, spinalized and paralyzed rabbits, intravenous administration 
      of the 5-HT1A-receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin 
      (8-OH-DPAT, 3-300 nmol kg(-1), cumulative) and flesinoxan (22-2200 nmol kg(-1), 
      cumulative) significantly increased the short latency reflex evoked in 
      gastrocnemius medialis motoneurones by electrical stimulation of all myelinated 
      afferents (Abeta and Adelta fibres) of the sural nerve. Reflexes increased to 
      median values of 198% (inter-quartile range (IQR) 148-473%) and 296% (IQR 
      254-522%) of pre-drug values with the highest doses of 8-OH-DPAT and flesinoxan, 
      respectively. The enhancement of reflexes induced by 5-HT1A-receptor agonists was 
      not reversed by the selective 5-HT1A-receptor antagonist (S)WAY-100135 (2.05 
      micromol kg[-1]). 2. The effects of 8-OH-DPAT were tested after pretreatment with 
      (S)WAY-100135 (2.05 micromol kg[-1]), its more potent analogue WAY-100635 (185 
      nmol kg[-1]), and the 5-HT2/5-HT1D-/5-HT7-receptor ligand ritanserin (1.67 
      micromol kg[-1]). 8-OH-DPAT (300 nmol kg(-1) single dose) significantly increased 
      gastrocnemius reflex responses in the presence of (S)WAY-100135 and WAY-100635, 
      to median values of 260% (IQR 171-295%) and 165% (IQR 136-170%) of pre-drug 
      levels, respectively. These values were not significantly different from each 
      other, or from the effects of 8-OH-DPAT given alone. When 8-OH-DPAT was given 
      after ritanserin, reflexes were a median of 102% (IQR 76-148%) of pre-drug 
      values: i.e. there was no significant increase in responses. Neither WAY-100635 
      nor ritanserin had any effects on reflexes per se. 3. WAY-100635 (185 nmol 
      kg[-1]) and ritanserin (1.67 micromol kg[-1]) were given after 8-OH-DPAT (300 
      nmol kg[-1]). The agonist increased reflexes to a median value of 184% (IQR 
      135-289%), after which WAY-100635 significantly reduced responses to 165% (IQR 
      130-254%) and ritanserin further decreased reflexes to a median of 107% (IQR 
      100-154%) of pre-drug levels, i.e. not significantly different from controls. 4. 
      Previous studies have shown that reflexes evoked by large myelinated axons tend 
      to be suppressed, rather than enhanced, by 5-HT1A-receptor agonists. When tested 
      against reflexes evoked by stimulation of the sural nerve at strengths between 
      1.5 and 2.5 times threshold, 8-OH-DPAT (3-300 nmol kg(-1), cumulative) and 
      flesinoxan (22-2200 nmol kg(-1), cumulative) significantly reduced gastrocnemius 
      responses to median values of 36% (IQR 15-75%) and 17% (IQR 12-38%) of pre-drug 
      levels, respectively. This inhibition was fully reversed by (S)WAY-100135 (2.05 
      micromol kg[-1]). 5. These data show that drugs that are agonists at 
      5-HT1A-receptors increase polysynaptic spinal reflexes evoked by moderate to high 
      stimulus intensities and depress responses to very low intensity stimuli. The 
      inhibitory effects of these drugs were mediated through 5-HT1A-receptors as they 
      were abolished by a selective antagonist for these sites. However, the 
      facilitatory effects of 8-OH-DPAT could be completely blocked only by a 
      combination of ritanserin, which has no significant affinity for 
      5-HT1A-receptors, with WAY-100635. It appears that the enhancement of reflexes by 
      8-OH-DPAT arises from a combined action at 5-HT1A-receptors and other, 
      ritanserin-sensitive, sites which could be 5-HT1D- or 5-HT7-receptors.
FAU - Clarke, R W
AU  - Clarke RW
AD  - School of Biology, University of Nottingham, Sutton Bonington Campus, 
      Loughborough.
FAU - Ogilvie, J
AU  - Ogilvie J
FAU - Houghton, A K
AU  - Houghton AK
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Receptors, Serotonin, 5-HT1)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/*pharmacology
MH  - Animals
MH  - Decerebrate State
MH  - Electric Stimulation
MH  - Female
MH  - Male
MH  - Rabbits
MH  - Receptors, Serotonin/*drug effects/physiology
MH  - Receptors, Serotonin, 5-HT1
MH  - Reflex/*drug effects/physiology
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Spinal Cord/*drug effects/physiology
MH  - Sural Nerve/physiology
PMC - PMC1564987
EDAT- 1998/01/10 00:00
MHDA- 1998/01/10 00:01
PMCR- 1998/10/01
CRDT- 1998/01/10 00:00
PHST- 1998/01/10 00:00 [pubmed]
PHST- 1998/01/10 00:01 [medline]
PHST- 1998/01/10 00:00 [entrez]
PHST- 1998/10/01 00:00 [pmc-release]
AID - 0701430 [pii]
AID - 10.1038/sj.bjp.0701430 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1997 Oct;122(4):631-8. doi: 10.1038/sj.bjp.0701430.