Reinforcing effect

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

In humans, a comparative examination of the positive reinforcing effects of solvents showed that among inhalant-dependent subjects, solvents induced a more intense sensation of pleasant feelings than that induced by alcohol and nicotine in subjects addicted to these substances (Kono et al. 2001). Solvent-dependent subjects reported pleasant feelings comparable to those reported by stimulant-dependent subjects after use of methamphetamine. However, 

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Hot tack strength is the abiUty of a heat-seal layer to hold together while molten, before the seal cools and sets up. This is a technically important property which is difficult to measure reproducibly in the laboratory. Owing to the reinforcing effect of ionic bonding on melt strength, ionomer sealing layers provide superior performance in a wide spectmm of appHcations. 

Finally, the combined reinforcing effect and high absorption capacity of asbestos fibers have been exploited in a variety of appHcations to increase dimensional stabiHty, typically in vinyl or asphalt tiles and asphalt toad surfacing. Figure 9 summarizes, as of 1984, the various classes of application for asbestos fibers in combination with other materials. The diagram shows that in recent years, most industrial appHcations have evolved towards composite materials where the fibers are bonded within an organic or inorganic matrix. 

The more the rubber present, the greater the reinforcing effect. The toughening does, however, appear to depend more on the number of particles of rubber than on the total volume of rubber present. 

For equivalent particle size the carbon blacks are the most powerful reinforcing fillers. However, fine particle size silicas can be very useful in non-black compounds whilst other fillers such as aluminium hydroxide, zinc oxide and calcium silicate have some reinforcing effect. 

The tensile properties of the extruded blends and composites are presented in Table 2. Compared to the neat PP, a clear reinforcement was achieved after twin-screw blending. The reinforcing effect was even more pronounced with the higher take-up speed (H), evidently due to the extremely fibrillar morphology, as seen in Fig. 3. 

The data given in Table 2 show that fibrous fillers have the optimum shape in terms of the maximum reinforcing effect, as could be expected. 

Opioid systems in the brain are important for the reinforcing effects of ethanol. Selective p-opioid receptor antagonists reliably decrease ethanol drinking in rats. 

The pharmacodynamic effects of ethanol are complex, and any attempt to link its actions to specific neurotransmitters or isolated brain regions is simplistic. A complicated neural network involved in the actions of ethanol accounts for its reinforcing, intoxicating, and abstinence effects. At the present time, use of medications that target neurotransmitters and neuromodulators affected by ethanol represents a reasonable strategy for the development of pharmacotherapies that reduce the reinforcing effects of alcohol and the craving and withdrawal symptoms that commonly occur in the context of alcohol dependence. 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

Ator NA Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, Zolpidem, and imidazenil in baboons. Psychopharmacology (Berl) 163 477 87, 2002... 

Mumford GK, Rush CR, Griffiths RR Abecarnil and alprazolam in humans behavioral, subjective and reinforcing effects. J Pharmacol Exp Ther 272 570-580, 1995b... 

Caffeine and nicotine have more complex reinforcing effects on dopamine. Caffeine, a methylxanthine compound, appears to exert its central ac-... 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

No systematic studies of tolerance to the reinforcing effects of inhaled nitrites have been reported. However, anecdotal observations in workers with high exposure to nitrites have suggested that tolerance to the subjective effects of this compound occurs after a few days of exposure (Marsh and Marsh... 

On the other hand, clinical and laboratory studies in humans have demonstrated the development of tolerance to the amnestic and analgesic effects of nitrous oxide and isoflurane (see Arnold et al. 1993 Avramov et al. 1990 Rupreht et al. 1985 Whitwam et al. 1976) and, in the case of ether or chloroform, to its reinforcing effects (Krenz et al. 2003). No studies have shown the development of tolerance to the reinforcing effects of nitrous oxide. 

Despite the paucity of systematic studies in humans, the available evidence suggests that, like drugs such as alcohol, sedatives, and stimulants, inhalant drugs (i.e., solvents, general anesthetics, and nitrites) exert reinforcing effects and increase motor activity. Furthermore, with continuous use, these drugs appear to induce both tolerance and symptoms of withdrawal. 

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