, 2001, 2002; De Wit & Stewart, 1981). The results obtained with [11C]raclopride binding confirm other reports in the literature but there were some surprises. Smoking denic cigarettes reduced inhibitor Nutlin-3a [11C]raclopride binding in the striatum as expected because of its cue-related smoking effects. One possibility is that the many chemicals in tobacco smoke with very small amounts of nicotine are important salience cues. Only some regions of the right hemisphere showed a significant increase in DA release with denic smoking when an uncorrected p < .001 was used. However, with a strict statistical criterion using a p FDR corrected to p < .02, smoking nic cigarettes increased striatal DA release but more on the left, consistent with previous research (Brody et al., 2004).

In the present study, only one region in the left caudate showed a weak (p < .05) correlation between an increase in plasma nicotine and increased DA release. Berridge, Espana, and Stalnaker (2004) described the brain asymmetry of DA efferents within the prefrontal cortex in regard to coping and stress in rodents. They suggested in humans that DA in the right hemisphere may play a unique role in affective and cognitive processes. Furthermore, right hemisphere damage in humans produces unique disorders of communication and cognition (Myers, 1999). In one word, the right brain is concerned with ��gestalt.�� The fact that nic smoking had marked bilateral striatal release effects, of which release DA in one area correlated with increased venous plasma nicotine, is further evidence of a pharmacological role of nicotine.

Marti et al. (2011) found that tobacco smoke extracts that contain nicotine, as well as nicotine alone, enhance triggered DA ventral tegmental area neurons in anesthetized wild type (WT) mice, but weak and inhibitory firing occurred with tobacco extracts. In ��2?/? knockout mice, nicotine or tobacco smoke had no effect on the firing patterns of DA neurons. However, the differences between DA neuron firing produced by tobacco extract/tobacco smoke or nicotine alone observed in the WT animals persisted in the ��6?/? mice but not in the ��4?/? mice. Marti et al. (2011) concluded that tobacco smoke or nicotine alone act through ��4��2 nicotinic cholinergic receptors (nAChRs) and that tobacco extract may contain unknown chemicals that antagonize the effects of nicotine.

Whether denic cigarette smoke contains substances that affect ��6?/? nAChRs needs further research. Entinostat Another important issue is whether the very low venous plasma nicotine levels after smoking denic cigarettes are sufficient to cause any brain effects. Brody et al. (2006) used the 18F derivative of A-85380, a selective PET ��4��2 nicotine cholinergic ligand, to demonstrate the effects of tobacco smoking on brain nAChRs. Smoking just one regular tobacco cigarette produced more than 88% receptor occupancy. A venous plasma nicotine concentration of only 0.