Marijuana and cannabinoid regulation of brain reward circuits.

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0007-1188 (Print) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Reward*; Brain/*physiology ; Cannabinoids/*pharmacology; Animals ; Brain/drug effects ; Cannabinoids/chemistry ; Humans ; National Institutes of Health (U.S.) ; United States

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

82

Arch Gen Psychiatry. 2001 Apr;58(4):322-8. (PMID: 11296091)
Mol Pharmacol. 2001 Jul;60(1):155-63. (PMID: 11408610)
Physiol Rev. 2003 Jul;83(3):1017-66. (PMID: 12843414)
Trends Neurosci. 2003 Aug;26(8):436-43. (PMID: 12900175)
Eur J Neurosci. 2003 Aug;18(3):524-34. (PMID: 12911748)
Psychopharmacology (Berl). 2003 Sep;169(2):115-34. (PMID: 12827346)
Drug Alcohol Rev. 2003 Dec;22(4):453-60. (PMID: 14660135)
J Neurosci. 2004 Jan 7;24(1):53-62. (PMID: 14715937)
Nat Neurosci. 2004 Jun;7(6):585-6. (PMID: 15146190)
Brain Res. 1995 Jun 5;682(1-2):215-21. (PMID: 7552315)
J Neurosci. 1996 May 1;16(9):3112-22. (PMID: 8622141)
Annu Rev Neurosci. 1996;19:319-40. (PMID: 8833446)
Psychopharmacology (Berl). 1996 Dec;128(4):413-20. (PMID: 8986012)
J Neurosci. 1997 Jan 1;17(1):11-22. (PMID: 8987732)
Neuroscience. 1997 Mar;77(1):155-66. (PMID: 9044383)
Neuroreport. 1997 Feb 10;8(3):649-52. (PMID: 9106740)
Neurosci Lett. 1997 May 2;226(3):159-62. (PMID: 9175591)
Science. 1997 Jun 27;276(5321):2048-50. (PMID: 9197269)
Neuroscience. 2001;106(1):1-4. (PMID: 11564411)
Trends Pharmacol Sci. 2001 Nov;22(11):565-72. (PMID: 11698100)
Nat Neurosci. 2001 Dec;4(12):1217-23. (PMID: 11694884)
Nat Neurosci. 2002 May;5(5):446-51. (PMID: 11976704)
Science. 2002 Apr 26;296(5568):678-82. (PMID: 11976437)
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8384-8. (PMID: 12060781)
Eur J Neurosci. 2002 Jun;15(12):2057-61. (PMID: 12099913)
Neuropharmacology. 2002 Sep;43(4):503-10. (PMID: 12367597)
Prog Neurobiol. 2002 Nov;68(4):247-86. (PMID: 12498988)
Chem Phys Lipids. 2002 Dec 31;121(1-2):267-90. (PMID: 12505706)
Neuron. 2003 Feb 20;37(4):577-82. (PMID: 12597856)
Trends Neurosci. 2003 Apr;26(4):184-92. (PMID: 12689769)
J Neurosci. 2003 Jun 15;23(12):4815-20. (PMID: 12832502)
J Neurosci. 1997 Jul 15;17(14):5271-80. (PMID: 9204911)
J Neurophysiol. 1997 Jul;78(1):43-50. (PMID: 9242259)
Pharmacol Ther. 1997;74(2):129-80. (PMID: 9336020)
Crit Rev Neurobiol. 1998;12(1-2):37-67. (PMID: 9444481)
Eur J Pharmacol. 1998 Jan 2;341(1):39-44. (PMID: 9489854)
J Neurophysiol. 1998 Apr;79(4):1768-76. (PMID: 9535946)
J Neurosci. 1998 Sep 1;18(17):7033-9. (PMID: 9712672)
J Neurosci. 1998 Oct 1;18(19):8003-15. (PMID: 9742167)
Eur J Neurosci. 1998 Sep;10(9):2825-30. (PMID: 9758152)
Eur J Pharmacol. 1998 Oct 16;359(1):1-18. (PMID: 9831287)
Neurobiol Dis. 1998 Dec;5(6 Pt B):502-33. (PMID: 9974181)
Nat Neurosci. 1999 May;2(5):467-72. (PMID: 10321252)
Behav Brain Res. 1999 Jun;101(2):129-52. (PMID: 10372570)
Life Sci. 1999;65(6-7):715-23. (PMID: 10462072)
Neuroscience. 1980;5(1):63-72. (PMID: 7366843)
Brain Res Bull. 1984 Feb;12(2):203-8. (PMID: 6609751)
Psychol Rev. 1987 Oct;94(4):469-92. (PMID: 3317472)
Psychiatr Med. 1985;3(4):445-60. (PMID: 2893431)
Neuroscience. 1988 Jan;24(1):19-28. (PMID: 3368048)
Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8. (PMID: 2899326)
Brain Res. 1988 Jun 7;451(1-2):59-68. (PMID: 2855215)
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6. (PMID: 2308954)
J Neurochem. 1990 Jul;55(1):21-6. (PMID: 2162376)
Nature. 1990 Aug 9;346(6284):561-4. (PMID: 2165569)
NIDA Res Monogr. 1990;97:79-93. (PMID: 2174124)
Psychopharmacology (Berl). 1990;102(2):156-62. (PMID: 2177204)
J Neurosci. 1991 Feb;11(2):563-83. (PMID: 1992016)
Neuroscience. 1991;41(1):89-125. (PMID: 2057066)
J Neurosci. 1992 Feb;12(2):483-8. (PMID: 1346804)
Pharmacol Biochem Behav. 1991 Nov;40(3):571-80. (PMID: 1806947)
Neurosci Lett. 1992 Jan 6;134(2):207-11. (PMID: 1350333)
Science. 1992 Oct 23;258(5082):665-7. (PMID: 1329209)
J Comp Neurol. 1993 Jan 22;327(4):535-50. (PMID: 8440779)
Brain Res. 1993 Sep 3;621(1):65-70. (PMID: 8221074)
FEBS Lett. 1994 Aug 22;350(2-3):240-4. (PMID: 8070571)
Neurosci Lett. 1995 Feb 17;186(2-3):91-4. (PMID: 7777206)
Curr Opin Neurobiol. 1999 Dec;9(6):690-7. (PMID: 10607649)
Neurosci Biobehav Rev. 2000 Jan;24(1):85-105. (PMID: 10654664)
Neuropharmacology. 2000 Jan 28;39(3):391-8. (PMID: 10698005)
J Neurosci. 2000 Apr 1;20(7):2470-9. (PMID: 10729327)
Learn Mem. 2000 May-Jun;7(3):132-9. (PMID: 10837502)
Synapse. 2000 Jul;37(1):71-80. (PMID: 10842353)
Neuroscience. 2000;99(4):661-7. (PMID: 10974429)
Synapse. 2000 Nov;38(2):114-23. (PMID: 11018785)
Nat Neurosci. 2000 Nov;3(11):1073-4. (PMID: 11036260)
J Neurosci. 2001 Jan 1;21(1):109-16. (PMID: 11150326)
J Neurophysiol. 2001 Jan;85(1):72-83. (PMID: 11152707)
Eur J Pharmacol. 2001 Jan 26;412(2):R3-5. (PMID: 11165232)
Nature. 2001 Mar 29;410(6828):588-92. (PMID: 11279497)

0 (Cannabinoids)

Date Created: 20040818 Date Completed: 20050422 Latest Revision: 20181113

20231215

PMC1575338

10.1038/sj.bjp.0705931

15313883