PMID- 9932709
OWN - NLM
STAT- MEDLINE
DCOM- 19990324
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 364
IP  - 2-3
DP  - 1999 Jan 8
TI  - Blockade of accumbens 5-HT3 receptor down-regulation by ondansetron administered 
      during continuous cocaine administration.
PG  - 79-87
AB  - The present experiment examined whether ondansetron, co-administered with 
      continuous cocaine, would block the down regulation of accumbens 5-HT3 receptors. 
      Rats were exposed to a 14-day pretreatment regimen that involved the continuous 
      infusion of 40 mg kg(-1) day(-1) cocaine or 0.9% saline via a subcutaneously 
      implanted osmotic minipump. In addition to the continuous cocaine or saline 
      administration, all subjects received daily subcutaneous (s.c.) injections of 
      either vehicle or 0.1 mg kg(-1) ondansetron for the entire 14-day pretreatment 
      regimen. The rats were then withdrawn from this pretreatment regimen for seven 
      days, and slices from the nucleus accumbens obtained. The slices were perfused 
      with 25 mM K+ in the absence and presence of 0, 12.5, 25, or 50 microM 
      m-Chlorophenyl-biguanide HCl (mCPBG). The efflux samples were assayed for 
      dopamine content by high pressure liquid chromatography (HPLC) with 
      electrochemical detection. Continuous cocaine administration significantly 
      attenuated the ability of mCPBG to facilitate K+-induce dopamine overflow 
      compared to saline control rats. In addition, the rats that received ondansetron 
      and cocaine during the 14-day pretreatment period, the ability of mCPBG to 
      enhance K+ stimulated dopamine release was not significantly different from the 
      saline control subjects. For all groups except the cocaine alone group, the 
      effects of mCPBG on K+ stimulated dopamine release were Ca2+ dependent, 
      suggesting that these effects are receptor mediated. These results suggest that 
      continuous cocaine administration functionally down-regulates 5-HT3 receptors in 
      the nucleus accumbens, and that this down-regulation can be blocked by chronic 
      ondansetron administration. Hence, a functional down regulation of accumbens 
      5-HT3 receptors represents a significant contribution to the tolerance induced by 
      continuous cocaine administration.
FAU - King, G R
AU  - King GR
AD  - Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. 
      gking@hsc.unt.edu
FAU - Xiong, Z
AU  - Xiong Z
FAU - Ellinwood, E H
AU  - Ellinwood EH
LA  - eng
GR  - 1R01DA10468/DA/NIDA NIH HHS/United States
GR  - 1R29-08899/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Biguanides)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Receptors, Serotonin, 5-HT3)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 4AF302ESOS (Ondansetron)
RN  - 910A4X901V (1-(3-chlorophenyl)biguanide)
RN  - I5Y540LHVR (Cocaine)
RN  - RWP5GA015D (Potassium)
RN  - SY7Q814VUP (Calcium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Biguanides/pharmacology
MH  - Brain/drug effects/metabolism
MH  - Calcium/pharmacology
MH  - Cocaine/*pharmacology
MH  - Dopamine/metabolism
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - In Vitro Techniques
MH  - Infusion Pumps
MH  - Injections, Subcutaneous
MH  - Male
MH  - Ondansetron/*pharmacology
MH  - Potassium/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*drug effects
MH  - Receptors, Serotonin, 5-HT3
MH  - Serotonin Antagonists/*pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
EDAT- 1999/02/05 00:00
MHDA- 1999/02/05 00:01
CRDT- 1999/02/05 00:00
PHST- 1999/02/05 00:00 [pubmed]
PHST- 1999/02/05 00:01 [medline]
PHST- 1999/02/05 00:00 [entrez]
AID - S0014-2999(98)00795-X [pii]
AID - 10.1016/s0014-2999(98)00795-x [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1999 Jan 8;364(2-3):79-87. doi: 10.1016/s0014-2999(98)00795-x.