Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependence.
Saturnino Spiga, Alessandra Lintas, Michele Migliore, Marco Diana
Addiction Biology July 2010 DOI: 10.1111/j.1369-1600.2010.00218.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats treated chronically with cannabinoid agonists and withdrawn |
| Interventions | Delta(9)-tetrahydrocannabinol CP55 940 SR141716A |
| Topics | Addiction Cannabis |
| Key findings | Withdrawal from chronic Delta(9)-tetrahydrocannabinol or CP55 940 reduced tyrosine hydroxylase-positive neurons in the ventrotegmental area and spine density in the nucleus accumbens shell, but not in the substantia nigra pars compacta or accumbens core. The authors argue these changes, modeled to reduce medium spiny neuron excitability, support a hypodopaminergic state in cannabinoid dependence. |
Abstract
Cannabinoid 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with two structurally different cannabinoid agonists, Delta(9)-tetrahydrocannabinol and CP55 940 (CP) rats were withdrawn spontaneously and pharmacologically with the CB1 antagonist SR141716A (SR).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revealed significant morphometrical reductions in the ventrotegmental area but not substantia nigra pars compacta of withdrawn rats.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sections of the nucleus accumbens revealed a decrease in the shell, but not the core, of the spines' density of withdrawn rats.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'.
Comparable studies
Other preclinical and animal studies on cannabis for addiction, most cited first.
Citations in the library
Cited by 2
- THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity. Synapse March 2018
- Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons in the striatum. PLoS One 2018
Cites 5
- Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addiction Biology June 2008
- Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure. Journal of Neuroscience December 14, 2005
- Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. Journal of Neuroscience June 15, 2003
- Abstinence symptoms following oral THC administration to humans. Psychopharmacology February 1, 1999
- Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proceedings of the National Academy of Sciences August 18, 1998