Withdrawal behaviors

Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray. J Neurosci 1997 17 8520-8527. 

Increased ACh release in NAcc Mec-precipitated somatically expressed withdrawal behaviors Rada et al. (2001)... 

Mec-precipitated somatically expressed withdrawal behaviors Mec-precipitated somatically expressed withdrawal behaviors Mec-precipitated somatically expressed withdrawal behaviors Naloxone-precipitated somatically expressed withdrawal behaviors Somatically expressed behaviors precipitated by mec in VTA less threshold changes induced by DA antagonist SCH3390-Withdrawal precipitated by systemic mec Spontaneous withdrawal... 

Mec-precipitated somatically expressed withdrawal behaviors Hippocampal slice from rats in spontaneous withdrawal Spontaneous withdrawal from cigarette smoking Spontaneous withdrawal from nicotine self-administration Spontaneous withdrawal... 

Somatically expressed withdrawal behaviors and condition place... 

The pattern of data on the role of al receptors (pentamers of the al subunit) is far from clear. Nomikos et al. (1999) reported sharply reduced locomotor activity in nicotine-dependent rats injected with the selective al antagonist methyl-lycaconitine (MLA). Barik and Wonnacott (2006) found increased al sensitivity in the hippocampus of rats during nicotine withdrawal, as evidence by increased norepinephrine release in response to an al agonist. On the other hand, Markou and Paterson (2001) reported that systemically administered ML A failed to precipitate either somatically expressed withdrawal behaviors or altered ICSS thresholds. 

There have been few studies of acetylcholine release during nicotine withdrawal. Rada et al. (2001) found that withdrawal from continuous nicotine infusion resulted in significantly increased acetylcholine release in the NAcc, concomitant with somatically expressed withdrawal behaviors. This was similar to the effect of morphine withdrawal on NAcc acetylcholine release. Since dopamine release was decreased at the same time, the transmitter balance in the NAcc was radically altered. 

The endocannabinoid system might also be involved, since A9-tetrahydorcan-nabinol, the major active ingredient in cannabis, decreases somatically expressed withdrawal behaviors and the aversiveness of withdrawal in mecamylamine- and naloxone-precipitated nicotine abstinence (Balfour 2002). However, genetic knockout of the CBl cannabinoid receptors did not significantly affect somatically expressed withdrawal behaviors (Castane et al. 2002). 

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... 

Several natural products have been evaluated in rodent models of nicotine withdrawal. An extract of Hypericum perforatum (St. John s Wort, a putative antidepressant, and inhibitor of serotonin reuptake) reversed somatically expressed withdrawal behaviors and locomotor depression in spontaneous withdrawal (Catania et al. 2003). A benzoflavone compound isolated from Passiflora incarnata, interfered with the induction of physical dependence. Coadministration with chronic nicotine prevented various subsequent indicators of withdrawal syndrome in the mouse, including jumping, locomotor inactivity, immobility in the swim test and naloxone-precipitated escape jumping (Dhawan et al. 2002). 

Ward HE, Johnson EA, Salm AK, Birkle DL (2000) Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav 70 359-366... 

Pierce and Raper (1995) studied the effects of laboratory handling procedures on naloxone-precipitated withdrawal behavior in morphine-dependent rats and Gellert and Holtzman (1978) used access to drug in drinking solutions to study morphine dependence and withdrawal in rats. 

Rodriguez de Fonseca, F, Rubio, R, Menzaghi, F, Merlo-Rich, E., Rivier, J., Koob, G.E and Navarro, M. (1996) Corticotropin-releasing factor (CRF) antagonist [D-Rhe Nle , C Melxtf ]CRE attenuates the acute actions of the highly potent cannabinoid receptor agonist HU-210 on defensive-withdrawal behavior in rats, J Pharmacol Exp Ther, 276 56-64. 

Phel2,Nle21,38,C alpha MeLeu37]CRF attenuates the acute actions of the highly potent cannabinoid receptor agonist HU-210 on defensive-withdrawal behavior in rats, J Pharmacol. Exp. Ther. 216, 56-64. 

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