, 1999). The implications of this kind of drug interaction are significant, potentially impacting tobacco awareness programs as well as the treatment of alcohol abuse disorders. For example, should

alcoholics be advised to abstain from tobacco as a means to reduce their drinking? Perhaps a pharmaceutical intervention could discourage excessive drinking among smokers. In pursuit of these ideas, in this issue of Neuron, Doyon et al. (2013) seek to uncover the mechanism by which tobacco use promotes alcohol consumption. They show that a single exposure to nicotine can cause drug-naive rats to self-administer more ethanol over 4 subsequent days than they otherwise would. Doyon et al. (2013) then carefully track down the mechanism underlying this effect and find the culprit to be nicotine-induced selleck chemicals llc increases in stress hormones

acting in the ventral tegmental area. At the center of this study is the regulation of synaptic inputs to dopamine neurons in the midbrain. First, Doyon et al. (2013) confirmed that nicotine and ethanol are both capable of augmenting dopamine Volasertib concentration levels in the nucleus accumbens. They also found that when administered together, the drugs produced additive effects on dopamine levels, consistent with their somewhat divergent mechanisms of regulating dopamine neuron activity (Fagen et al., 2003 and Söderpalm and Ericson, 2013). When nicotine was administered first, however, 3–40 hr prior, ethanol-induced increases in dopamine levels were significantly attenuated. Importantly, nicotine pretreatment did not alter dopaminergic responses to subsequent nicotine injections, indicating that this dopaminergic circuitry is generally capable crotamiton of responding to drugs in a consistent manner. The extended time window during which these nicotine-ethanol interactions were observed, when dopaminergic responses to ethanol were blunted, coincided with the period when nicotine-exposed animals increased their ethanol intake. This

connection is somewhat counterintuitive, that ethanol self-administration rates would rise precisely when dopamine neurons exhibit a muted response to ethanol. However, a blunted dopamine system has previously been associated with increased susceptibility to alcohol abuse (Martinez et al., 2005). There is also evidence that animals self-administer drugs of abuse at a frequency necessary to maintain a specific elevated level of dopamine (Ranaldi et al., 1999), suggesting that the nicotine-pretreated rats may have increased their drinking to compensate for the diminished potency of ethanol on dopaminergic signaling. Ethanol is believed to augment dopamine levels in the nucleus accumbens by increasing the firing rate of ventral tegmental area dopamine neurons. Using brain slice electrophysiology, Doyon et al. (2013) confirmed that bath application of ethanol increases the excitatory drive onto midbrain dopamine neurons, as well as their average firing rate.

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