[Abstract Title]. - Society for Neuroscience

Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.1/AA4
Topic: C.16.l. Addiction: Neurobiology
Support: Philip Morris USA Inc.
Title: Inhibition of anandamide hydrolysis blocks nicotine, but not morphine and cocaine, effects
on mesolimbic dopamine neurons
Authors: *A. MUNTONI 1 , G. PILLOLLA 2 , A. LUCHICCHI 2 , M. MELIS 2 , M. PISTIS 2 ;
1 Inst. of Neurosci., CNR, Cagliari, Italy; 2 B.B. Brodie Dept of Neuroscience, Univ. of Cagliari,
Cagliari, Italy
Abstract: Increasing evidence suggests that the endogenous cannabinoid (endocannabinoid)
system is involved in the general neurobiological substrates underlying drug addiction and in the
mechanisms of action of different drugs, including nicotine, opiates and psychostimulants. For
instance, it has been shown that pharmacological blockade or genetic ablation of cannabinoid
receptors type-1 (CB1) decreases nicotine and opiates self-administration, while acute
administration of cocaine increases the levels of the endocannabinoid anandamide in the
striatum. All these addictive drugs are well-known to interact with the mesolimbic dopamine
(DA) system, which arises from the ventral tegmental area (VTA) and is critical for the central
processing of reward and motivation. Here we investigated whether the enhancement of
endocannabinoid levels produced by the irreversible fatty acid amide hydrolase (FAAH)
inhibitor URB597 would affect modulation of VTA DA neurons by nicotine, morphine and
cocaine. To this aim, single unit extracellular recordings from VTA DA neurons were performed
in chloral hydrate anaesthetized rats. Animals were pre-treated with URB597, or vehicle, and
then the effects of nicotine, morphine or cocaine were studied on firing rate and discharge pattern
of VTA DA cells. As expected, nicotine (0.2 mg/kg i.v.) stimulated the firing rate and the
percent of burst firing of VTA DA neurons. On the other hand, in URB597 (0.1 mg/kg i.v., 1-2
hours before recordings) pre-treated animals, we observed a complete blockade of the excitation
induced by nicotine. Morphine also (4.0 mg/kg i.v.) increased the firing rate and the percent of
burst firing of VTA DA neurons, but its effects were not antagonized by URB597 pre-treatment.
Similarly, the inhibitory actions of cocaine (1.0 mg/kg, i.v.) on neuronal activity of VTA DA
cells were not prevented by URB597. These findings suggest that URB597 selectively
antagonizes nicotine-induced effects, being ineffective on morphine- and cocaine-evoked
excitation or inhibition, respectively, of DA neuronal activity. Thus, our data point to a specific
vulnerability of nicotinic acetylcholine receptors towards the negative modulation induced by