Nicotine withdrawal syndrome

Hildebrand BE, Nomikos GG, Hertel P, SchEstrom B, Svensson TH. 1998. Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779(1—2) 214-225. 

Panagis G, Hildebrand BE, Svensson TH, Nomikos GG. 2000. Selective c-fos induction and decreased dopamine release in the central nucleus of amygdala in rats displaying a meca-mylamine-precipitated nicotine withdrawal syndrome. 

Heimer L, Zahm DS, ChurchUl L, Kalivas PW, Wohltman C (1991) Specificity in the projection patterns of accumbal core and medial shell in the rat. Neuroscience 41 89-125 Hemby SE, No C, Koves TR, Smith JE, Dworkin SI (1997) Differences in extracellular dopamine concentration in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology 133 7-16 Hildebrand BE, Nomikos GG, Hertel P, Sclrilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not the prefrontal cortex in rats displaying mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779 214-225 Ikemoto S (2003) Involvement of the olfactory tubercle in cocaine reward intracranial selfadministration studies. J Neurosd 23 9305-9311... 

Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol... 

To what extent are the rodent models of nicotine physical dependence and nicotine withdrawal syndrome valid representations of physical dependence and withdrawal syndrome in hnman tobacco users Validity can only be partial at best because of species differences and differences in the means, dnration and composition of drug exposnre (nicotine alone versus tobacco smoke). The differences between the models and hnman tobacco use phenomena will always be as important as the analogies. 

The availability of rodent models of nicotine physical dependence and abstinence has made it possible to identify several anatomical regions that play a critical role in these phenomena. In reviewing the evidence, the multidimensional nature of the nicotine withdrawal syndrome should be considered, raising the possibility that different withdrawal signs and symptoms might be attributable to events in different anatomical regions. Table 2 summarizes a number of representative studies. There is some overlap with Table 3 on neurochemical mechanisms, since many studies cited there are studies of regional neurochemistry. 

Nicotine injection immediately reverses somatically expressed nicotine withdrawal syndrome (Malin et al. 1992), but it fails to do so after pretreatment with naloxone to block opiate receptors (Malin et al. 1996a). This suggests that nicotine relieves this aspect of nicotine withdrawal syndrome through inducing renewed release of endogenous opioid peptides. 

Early adolescent smoking onset is a risk factor for severe addiction and difficulty in smoking cessation in adulthood (Breslau and Peterson 1996). Therefore, it is significant that nicotine has more potent rewarding effects in adolescent as opposed to adult rodents (Adriani et al. 2004 Belluzzi et al. 2004 Vastola et al. 2002). However, several studies suggest that adolescent rodents develop physical nicotine dependence less readily than adults, as indicated by less severe nicotine withdrawal syndrome. Unlike adult rats, continuously nicotine-infused adolescent rats failed to display mecamylamine-precipitated withdrawal behaviors (O Dell et al. 2004, 2006). They also displayed less mecamylamine-precipitated conditioned place aversion than adults (O Dell etal. 2007). In addition, nicotine-infused adolescent rats experienced smaller mecamylamine-precipitated ICSS threshold elevations than adults (Kota et al. 2007). Nicotine-infused adolescent mice also displayed fewer spontaneous and mecamylamine-precipitated somatically expressed withdrawal behaviors... 

Suzuki T, Ise Y, Tsuda M, Maeda J, Misawa M (1996) Mecamylamine-precipitated nicotine-withdrawal aversion in rats, Eur J Pharmacol 314 281-284 Suzuki T, Ise Y, Mori T, Misawa M (1997) Attenuation of mecamylamine-precipitated nicotine-withdrawal aversion by the 5-HT3 receptor antagonist ondansetron. Life Sci 6LPL249-254 Tzavara ET, Monory K, Hanoune J, Nomikos GG (2002) Nicotine withdrawal syndrome behavioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala. Eur J Neurosci 16 149-153... 

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