Short communicationConcentration-dependent conditioned place preference to inhaled toluene vapors in rats
Introduction
Voluntary inhalation of volatile solvents found in inexpensive commercial products such as glues, paint products, cleaning fluids and lighter fluids is prevalent in industrialized cities throughout the world, especially amongst juveniles and adolescent children (Andersen and Loomis, 2003, Basu et al., 2004). However, despite the widespread nature of solvent-abuse, also termed “glue-sniffing” there have been relatively few studies aimed at developing animal models for the abuse of these substances, especially when compared with the extensive literature on animals models for the reinforcing properties of cocaine, opiates and alcohol (Tzschentke, 1998, Bardo and Bevins, 2000). Part of the explanation for this may be related to the fact that these solvents are abused by inhalation, making them hard to administer to animals in controlled amounts. Additionally, the CNS target site for abused-solvents has been less well defined than that for other drugs-of-abuse and this has deterred studies on the neurobiological basis for their reinforcing effects.
Toluene is a component of many of the commercial products used for solvent-abuse and has been the focus of much of the existing animal literature relating to this topic. The acute behavioral effects of toluene-intoxication in animals have been well documented and include ataxic gait, biphasic effects on motor activity and anxiolytic actions (Garriott et al., 1981, King, 1982, Wood et al., 1984, Balster, 1998, Bowen et al., 1999). In drug-discrimination studies toluene shows cross-generalization with ethanol and barbiturates (Rees et al., 1985, Rees et al., 1987, Knisely et al., 1990).
Animal models of the reinforcing effects of toluene have been studied in several diverse studies using both inhaled and intravenous routes of administration (Weiss et al., 1979, Riegel and French, 2002, Bespalov et al., 2003, Blokhina et al., 2004). We chose to model the inhaled route of administration, as this is directly relevant to the route of administration characteristic of recreational use. In our own studies (Gerasimov et al., 2003, Lee et al., 2004) and those by Yavich et al. (1994) and Funada et al. (2002), inhaled toluene produces a positive place preference in the conditioned place preference (CPP) model for drug-seeking behavior.
The purpose of the present investigation was to optimize the paradigm for producing CPP to toluene vapors in rats by investigating the effect of extra conditioning days and a broader range of toluene concentrations on the degree of place preference.
Section snippets
Subjects
Animal procedures were in accordance with the NIH guide for the care and use of all laboratory animals. Male Sprague–Dawley rats (150–250 g; Taconic Farms, Germantown, NY) were housed in pairs on a 12 h light/dark cycle.
Apparatus
The place preference box (ENV-013, MED Associates, Inc. St. Albans, VT) consisted of three distinct compartments separated by two guillotine doors. The walls of the middle chamber were gray (21 cm × 21 cm × 11 cm) with a smooth PVC floor while the outer conditioning compartments (21 cm × 21
Results
In the pre-conditioning tests animals showed no bias to either conditioning chamber with approximately equal time spent in the black and white sides of the box (black: 271 ± 10 s; white: 306 ± 4 s, p not significant (t-test)). As observed in our previous study (Gerasimov et al., 2003), the animals showed most preference for the central choice chamber (mean of 323 s). This may be related to the relatively enclosed space in this compartment compared to the larger, more open, pairing chambers.
Animals
Discussion
Rats will show a CPP for a variety of drugs that are abused by humans (Tzschentke, 1998, Bardo and Bevins, 2000). Cocaine, amphetamines, and opiates produce especially robust place preferences (Carr and White, 1986, Nomikos and Spyraki, 1988). Alcohol and nicotine will also produce conditioned place preferences (Shoaib et al., 1994, Risinger and Oakes, 1996). The data in the present study confirms previous reports (Yavich et al., 1994, Funada et al., 2002, Gerasimov et al., 2003, Lee et al.,
Acknowledgements
Supported by National Institute of Health grant DA017349 and performed under Brookhaven Science Associates contract No. DE-AC02-98CH10886 with the U.S. Department of Energy.
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