Nicotine self-administration induces CB1-dependent LTP in the bed nucleus of the stria terminalis.
Journal of Neuroscience. 2014-03-19; 34(12): 4285-4292
DOI: 10.1523/jneurosci.3149-13.2014
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Nicotine addiction is characterized by repetitive drug taking and drug seeking,
both tightly controlled by cannabinoid CB1 receptors. The responsiveness of
neurons of the bed nucleus of the stria terminalis (BNST) to infralimbic cortex
(ILCx) excitatory inputs is increased in rats with active, but not passive,
nicotine taking. Therefore, we hypothesize that acquisition of the learned
association between nicotine infusion and a paired cue light permits the
strengthening of the ILCx-BNST synapses after ILCx tetanic stimulation. We
exposed rats to intravenous nicotine self-administration for 2 months. Using a
combination of in vivo protocols (electrical stimulations, extracellular
recordings, and pharmacological manipulations), we characterized the effects of
10 Hz stimulation of the ILCx on BNST excitatory responses, under different
conditions of exposure to nicotine. In addition, we tested whether the effects of
the stimulation were CB1 receptor-dependent. The results show that nicotine
self-administration supports the induction of evoked spike potentiation in the
BNST in response to 10 Hz stimulation of ILCx afferents. Although not altered by
nicotine abstinence, this cellular adaptation was blocked by CB1 receptor
antagonism. Moreover, blockade of BNST CB1 receptors prevented increases in
time-out responding subsequent to ILCx stimulation and decreased cue-induced
reinstatement. Thus, the synaptic potentiation within the BNST in response to
ILCx stimulation seems to contribute to the cue-elicited responding associated
with nicotine self-administration and is tightly controlled by CB1 receptors.
DOI: 10.1523/JNEUROSCI.3149-13.2014
PMID: 24647948 [Indexed for MEDLINE]