Present address: Simona Perra, PhD, WCAAR, Department of Neurobiology, University of Texas at Austin, Austin, TX, 78712.
Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid System
Article first published online: 22 JAN 2008
© 2008 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 32, Issue 3, pages 443–449, March 2008
How to Cite
Perra, S., Pillolla, G., Luchicchi, A. and Pistis, M. (2008), Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid System. Alcoholism: Clinical and Experimental Research, 32: 443–449. doi: 10.1111/j.1530-0277.2007.00588.x
- Issue published online: 30 JAN 2008
- Article first published online: 22 JAN 2008
- Received for publication May 8, 2007; accepted November 16, 2007.
- Basolateral Amygdala;
Background: A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol.
Methods: We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens.
Results: Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 ± 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 ± 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose–response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 ± 16% of baseline firing at 0.5 g/kg, p < 0.05).
Conclusions: Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism.