Precipitated withdrawal

Mintzer MZ, Stoller KB, Griffiths RR A controlled study of flumazenil-precipitated withdrawal in chronic low-dose benzodiazepine users. Psychopharmacology (Berl) 147 200-209, 1999... 

Research on CBl knockout mice demonstrated the pivotal role of CBl receptors in cannabis dependence knockout mice have been shown not to self-administer cannabinoids (Ledent et al. 1999) and also to fail to exhibit symptoms ofSRl417l6A-precipitated withdrawal (Ledent et al. 1999 Lichtman et al. 2001). Although the research summarized earlier is consistent in reporting the occurrence of a variety of withdrawal symptoms following cessation of exposure to cannabinoids (which were injected), precipitated withdrawal in mice following chronic exposure to marijuana smoke was more recently reported (Lichtman and Martin 2002). 

Aceto MD, Scares SM, Lowe JA, et al Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. Eur J Pharmacol 282 R1-R2, 1995... 

Compton WM, Grant BF, Colliver JD, et al Prevalence of marijuana use disorders in the United States 1991-1992 and2001-2002. JAMA291 2114-2121,2004 Cook SA, Lowe JA, Martin BR CBl receptor antagonist precipitates withdrawal in mice exposed to delta9-tetrahydrocannabinol. J Pharmacol Exp Ther 285 1150— 1156, 1998... 

Lichtman AH, Wiley JL, LaVecchia KL, et al Acute and chronic cannabinoid effects characterization of precipitated withdrawal in dogs. Eur J Pharmacol 357 139-148, 1998... 

Lichtman AH, Sheikh SM, Loh HH, et al Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298 1007—1014, 2001... 

Most of the work has been based on opioids since it is the easiest system to manipulate as administration of the antagonist, naloxone, precipitates withdrawal. Flere, the idea that physical dependence results from opposing changes in the neuronal systems depressed by the drug of dependence is borne out by consideration of the acute effects of an opioid and the withdrawal symptoms. They are mirror images of each other ... 

Blasig, J. Hen, A. Reinhold, K. and Zieglgansberger, S. Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33 19-38, 1973. 

Wang, G.J., Volkow, N.D., Fowler, J.S. et al. Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal. Neuropsychopharmacology. 16 174, 1997. 

The answer is b. (Katzungr pp 806—807J Rifampin induces cytochrome P450 enzymes, which causes a significant increase in elimination of drugs, such as oral contraceptives, anticoagulants, ketoconazole, cyclosporine, and chloramphenicol. It also promotes urinary excretion of methadone, which may precipitate withdrawal. 

May precipitate withdrawal in opiate-depen-dent patients... 

Third-line agent for moderate-to-severe pain May precipitate withdrawal in opiate-depen-dent patients... 

Frances B, Gout R, Cros J, Zajac JM. (1992). Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice. Fundam Clin Pharmacol. 6(8-9) 327-32. 

Brain activity changes (measnred with fMRl) during cigarette withdrawal were recently reported for nicotine-dependent rats (Shoaib et al. 2004). In this study, subcutaneous mecamylamine (1 mg kg ), a nicotine receptor antagonist, was administered to precipitate withdrawal dnring scanning, and this state was compared to a control state after subcntaneons saline administration. After subcutaneous mecamylamine, nicotine-dependent rats had bilateral increases in NAc activity compared to the control state. 

Carboni and colleagues have reported that mecamylamine-precipitated withdrawal of nicotine increases DA overflow in the prefrontal cortex and have suggested that this increase in DA overflow may also contribute to the aversive consequences of abrupt nicotine withdrawal (Carboni et al. 2000). This response to nicotine withdrawal is not a universal finding since Hildebrand and colleagues failed to observe any changes in DA overflow in the prefrontal cortex following mecamylamine-precipitated withdrawal (Hildebrand et al. 1998). Thus, again, the putative role of these mesocortical projections in the behavioural responses to nicotine withdrawal remains unproven. 

Both spontaneous and lucotinic antagoiust-precipitated withdrawal have been widely used in both rats and mice. Spontaneous withdrawal is initiated by simply... 

Spontaneous or precipitated Withdrawal syndrome measures Some representative studies... 

Amygdala c-fos induction during mec-precipitated withdrawal Panagis et al. (2000)... 

Head-twitches in spontaneous and precipitated, withdrawal (mec and DH 3E) Yasuda et al. (2002)... 

Firing rate of substantia nigra DA neurons increased Recovery from depressed firing rate of VTA DA neurons D 1-like antagonist in amygdala doesn t precipitate withdrawal Reduced amygdala central nucleus DA... 

GABAergic mechanisms Increased diazepam binding inhibitor mRNA GABA-B agonist does not affect nicotine withdrawal Endocannobioids D9-tetrahydrocannobinol decreased mec- and naloxone-precipitated withdrawal... 

Naloxone precipitates nicotine withdrawal in mice Naloxone induces place aversion in nicotine-dependent rats Naloxone prevents nicotine alleviation of nic. withdrawal Mu and delta agonists reduced mec-precipitated aversion Kappa antagonist suppresses mec.-precipitated aversion P-Endorphin metabolite Gly-Glu blocks aversiveness of mec-precipitated withdrawal Mec precipitates hyperalgesia in nicotine-tolerant rats NAcc Met-enkephalin increased Striatum preproenkephalin mRNA increased... 

Carboni et al. (2000) reported increased DA output in the prefrontal cortex during mecamylamine-precipitated withdrawal. The striatum appears to become insensitive to nicotine during withdrawal, as indicated by loss of the cFos response to nicotine. This was also true of a limbic region, the cingulate gyrus (Salminen et al. 1999). 

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... 

Aiicioglu-Kartal F, Kayir H, Tayfun U1 (2003) Effects of harman and harmine on naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Life Sci 73 2363-2371 Balerio GN, Aso E, Berrendero E, Murtra P, Maldonado R (2004) Delta9- tetrahydrocanabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice, Eur J Neurosci 20 2737-2748... 

Fundamental distrust of the industry s ethics. The public realisation that research studies have been withheld from public view, or released in partial (and misleading) form, has created enormous pressures for industry to make information on all trials available via the internet. The delays in relabelling products, the precipitous withdrawal of widely marketed drugs and the failure to identify safety risks before approval (even when it was not scientifically possible to do so) gives support to the canard that companies put profits before people. And prosecutions of major companies for... 

---