Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependence.
by
Spiga S, Lintas A, Migliore M, Diana M.
Department of Animal Biology and Ecology,
University of Cagliari, Italy.
Addict Biol. 2010 May 11.
ABSTRACTCannabinoid withdrawal produces a hypofunction of mesencephalic dopamine neurons that impinge upon medium spiny neurons (MSN) of the forebrain. After chronic treatment with two structurally different cannabinoid agonists, Delta(9)-tetrahydrocannabinol and CP55 940 (CP) rats were withdrawn spontaneously and pharmacologically with the CB1 antagonist SR141716A (SR). In these two conditions, evaluation of tyrosine hydroxylase (TH)-positive neurons revealed significant morphometrical reductions in the ventrotegmental area but not substantia nigra pars compacta of withdrawn rats. Similarly, confocal analysis of Golgi-Cox-stained sections of the nucleus accumbens revealed a decrease in the shell, but not the core, of the spines' density of withdrawn rats. Administration of the CB1 antagonist SR to control rats, provoked structural abnormalities reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis by acting as eu-proliferative signals through the CB1 receptors. Further, these measures were incorporated into a realistic computational model that predicts a strong reduction in the excitability of morphologically altered MSN, yielding a significant reduction in action potential output. These pieces of evidence support the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system and provide direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their postsynaptic counterpart and are coherent with recent hypothesis underscoring a hypodopaminergic state as a distinctive feature of the 'addicted brain'.THC
Bliss
Aerosol
Memory
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Anandamide
Just say know
Tolerant mice
Counter-reward
Forgetful rodents
Endocannabinoids
Stoned as a newt?
The nectar of delight
Stoned chocaholics?
Rodent cannabis abuse
Cannabis and schizophrenia
Cannabinoids/Parkinson's disease
Cannabis use and dopamine risk factor for schizophrenia questioned01 02 03 04 05 06 07 08 09 10 11 12 13 14 15
Refs
HedWeb
Future Opioids
BLTC Research
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
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The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family
