PMID- 8344205
OWN - NLM
STAT- MEDLINE
DCOM- 19930903
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 133
IP  - 2
DP  - 1993 Aug
TI  - Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic 
      stimulation of prolactin secretion via 5-HT1c/2 receptors.
PG  - 661-7
AB  - These studies examined the hypothalamic site and receptor subtype mediating the 
      serotonergic (5-HT) control of PRL secretion in conscious male rats. Initially, 
      we characterized the pharmacology of the 5-HT releaser and 5-HT agonists that 
      increase PRL release. Subsequently, we performed lesion experiments to locate the 
      5-HT receptors involved in PRL secretion. p-Chloroamphetamine, a 5-HT releaser, 
      is postulated to enter serotonergic nerve terminals through the 5-HT uptake 
      mechanism, which can be inhibited by fluoxetine. p-Chloroamphetamine (8 mg/kg, 
      ip) increased the plasma PRL concentration approximately 6-fold. The 5-HT uptake 
      inhibitor fluoxetine almost completely prevented this increase, demonstrating 
      that p-chloroamphetamine increases PRL release via a serotonergic mechanism. The 
      5-HT1C/5-HT2 agonist +(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl (ip) 
      produced a strong (30-fold) dose-dependent elevation of plasma PRL, which was 
      virtually eliminated by 0.1 mg/kg (sc) ritanserin, a 5-HT1C/5-HT2 antagonist. 
      +(-)-1-(2,5-Dimethoxy-4-iodophenyl)2-aminopropane HCl injected 
      intracerebroventricularly (icv) in doses below those that were peripherally 
      effective also produced a significant (8-fold) increase in PRL secretion that was 
      again attenuated by icv pretreatment with ritanserin (2 micrograms/kg). RU 24969 
      (5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]1H-indole) was reported to act as 
      both a 5-HT releaser and a direct postsynaptic 5-HT agonist. To test whether RU 
      24969 releases 5-HT to increase PRL secretion, we depleted 5-HT stores with the 
      5-HT synthesis inhibitor p-chlorophenylalanine. The ability of RU 24969 (0.5, 1, 
      5, and 10 mg/kg, ip) to elevate PRL secretion was not inhibited by pretreatment 
      with p-chlorophenylalanine, suggesting that RU 24969 stimulates PRL secretion 
      only through activation of postsynaptic 5-HT receptors. To test whether RU 24969 
      acts centrally, it was injected either icv, through chronic icv cannulae, or 
      peripherally (ip). RU 24969 injected icv significantly stimulated PRL secretion 
      (11-fold) at doses 500-fold lower than the peripherally effective doses (10 
      micrograms/kg vs. 5 mg/kg), suggesting a role for central 5-HT receptors in the 
      regulation of PRL secretion. In addition, rats pretreated with the 5-HT1C/5-HT2 
      antagonist LY53857 (icv) significantly inhibited the PRL response if RU 24969 was 
      injected ip, but not icv. The results of these experiments suggest that 5-HT1C or 
      5-HT2 receptors in the brain participate in the serotonergic stimulation of PRL 
      secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Rittenhouse, P A
AU  - Rittenhouse PA
AD  - Department of Pharmacology, Boston University Medical Center, Massachusetts 
      02118.
FAU - Levy, A D
AU  - Levy AD
FAU - Li, Q
AU  - Li Q
FAU - Bethea, C L
AU  - Bethea CL
FAU - Van de Kar, L D
AU  - Van de Kar LD
LA  - eng
GR  - DA-04865/DA/NIDA NIH HHS/United States
GR  - MH-45812/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Amphetamines)
RN  - 0 (Ergolines)
RN  - 0 (Indoles)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 2552-55-8 (Ibotenic Acid)
RN  - 2ISE72RACC (5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole)
RN  - 333DO1RDJY (Serotonin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - 9002-62-4 (Prolactin)
RN  - L37TVX7U5M (LY 53857)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
SB  - IM
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Ergolines/pharmacology
MH  - Ibotenic Acid/pharmacology
MH  - Indoles/pharmacology
MH  - Male
MH  - Neurons/*physiology
MH  - Paraventricular Hypothalamic Nucleus/drug effects/*physiology
MH  - Prolactin/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*physiology
MH  - Serotonin/*physiology
MH  - Serotonin Receptor Agonists/pharmacology
MH  - p-Chloroamphetamine/pharmacology
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
AID - 10.1210/endo.133.2.8344205 [doi]
PST - ppublish
SO  - Endocrinology. 1993 Aug;133(2):661-7. doi: 10.1210/endo.133.2.8344205.