PMID- 22692568
OWN - NLM
STAT- MEDLINE
DCOM- 20130226
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 11
DP  - 2012 Oct
TI  - Chronic Delta(9)-tetrahydrocannabinol exposure induces a sensitization of dopamine D(2)/(3) 
      receptors in the mesoaccumbens and nigrostriatal systems.
PG  - 2355-67
LID - 10.1038/npp.2012.91 [doi]
AB  - Delta(9)-tetrahydrocannabinol (THC), through its action on cannabinoid type-1 receptor 
      (CB(1)R), is known to activate dopamine (DA) neurotransmission. Functional evidence 
      of a direct antagonistic interaction between CB(1)R and DA D(2)-receptors (D(2)R) 
      suggests that D(2)R may be an important target for the modulation of DA 
      neurotransmission by THC. The current study evaluated, in rodents, the effects of 
      chronic exposure to THC (1 mg/kg/day; 21 days) on D(2)R and D(3)R availabilities 
      using the D(2)R-prefering antagonist and the D(3)R-preferring agonist radiotracers 
      [(1)(8)F]fallypride and [(3)H]-(+)-PHNO, respectively. At 24 h after the last THC dose, 
      D(2)R and D(3)R densities were significantly increased in midbrain. In 
      caudate/putamen (CPu), THC exposure was associated with increased densities of 
      D(2)R with no change in D(2)R mRNA expression, whereas in nucleus accumbens (NAcc) 
      both D(3)R binding and mRNA levels were upregulated. These receptor changes, which 
      were completely reversed in CPu but only partially reversed in NAcc and midbrain 
      at 1 week after THC cessation, correlated with an increased functionality of 
      D(2)/(3)R in vivo, based on findings of increased locomotor suppressive effect of a 
      presynaptic dose and enhanced locomotor activation produced by a postsynaptic 
      dose of quinpirole. Concomitantly, the observations of a decreased gene 
      expression of tyrosine hydroxylase in midbrain together with a blunted 
      psychomotor response to amphetamine concurred to indicate a diminished 
      presynaptic DA function following THC. These findings indicate that the early 
      period following THC treatment cessation is associated with altered presynaptic 
      D(2)/(3)R controlling DA synthesis and release in midbrain, with the concurrent 
      development of postsynaptic D(2)/(3)R supersensitivity in NAcc and CPu. Such D(2)/(3)R 
      neuroadaptations may contribute to the reinforcing and habit-forming properties 
      of THC.
FAU - Ginovart, Nathalie
AU  - Ginovart N
AD  - University Department of Psychiatry, University of Geneva, Geneva, Switzerland. 
      nathalie.ginovart@unige.ch
FAU - Tournier, Benjamin B
AU  - Tournier BB
FAU - Moulin-Sallanon, Marcelle
AU  - Moulin-Sallanon M
FAU - Steimer, Thierry
AU  - Steimer T
FAU - Ibanez, Vicente
AU  - Ibanez V
FAU - Millet, Philippe
AU  - Millet P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120613
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (2-phytyl-1,4-naphthoquinone)
RN  - 0 (Benzamides)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 10028-17-8 (Tritium)
RN  - 20OP60125T (Quinpirole)
RN  - 7J8897W37S (Dronabinol)
RN  - 84-80-0 (Vitamin K 1)
RN  - CK833KGX7E (Amphetamine)
RN  - G9FWZ369GX (fallypride)
SB  - IM
MH  - Amphetamine/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Basal Ganglia/diagnostic imaging/drug effects/*metabolism
MH  - Benzamides/pharmacokinetics
MH  - Dopamine Agonists/pharmacology
MH  - Dopamine Antagonists/pharmacokinetics
MH  - Dopamine Uptake Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dronabinol/*pharmacology
MH  - Drug Interactions
MH  - Fluorodeoxyglucose F18/pharmacokinetics
MH  - Gene Expression Regulation/drug effects
MH  - Locomotion/drug effects
MH  - Male
MH  - Nucleus Accumbens/diagnostic imaging/*drug effects/metabolism
MH  - Positron-Emission Tomography
MH  - Protein Binding/drug effects
MH  - Psychotropic Drugs/*pharmacology
MH  - Quinpirole/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/genetics/*metabolism
MH  - Tritium/pharmacokinetics
MH  - Vitamin K 1/analogs & derivatives/pharmacokinetics
PMC - PMC3442351
EDAT- 2012/06/14 06:00
MHDA- 2013/02/27 06:00
PMCR- 2013/10/01
CRDT- 2012/06/14 06:00
PHST- 2012/06/14 06:00 [entrez]
PHST- 2012/06/14 06:00 [pubmed]
PHST- 2013/02/27 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - npp201291 [pii]
AID - 10.1038/npp.2012.91 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 Oct;37(11):2355-67. doi: 10.1038/npp.2012.91. Epub 
      2012 Jun 13.