Review article The last decade of solvent research in animal models of abuse: Mechanistic and behavioral studies ☆ Scott E. Bowen a,b, ⁎ ,1 , Jeffery C. Batis a , Nayeli Paez-Martinez c , Silvia L. Cruz c, ⁎ ,1 a Department of Psychology, Wayne State University 5057 Woodward, Detroit, MI, 48202, USA b Department of Obstetrics and Gynecology, Wayne State University 5057 Woodward, Detroit, MI, 48202, USA c Departamento de Farmacobiologia, Cinvestav, IPN Calz. De los Tenorios 235, Col. Granjas Coapa Mexico D.F. 14330, Mexico Received 7 August 2006; received in revised form 8 September 2006; accepted 9 September 2006 Available online 20 September 2006 Abstract The Last Decade of Animal solvent Abuse Research: Mechanistic and Behavioral Studies. Bowen, S. E., Batis, J.C., Paez-Martinez, N., and Cruz, S.L. Neurotoxicology and Teratology , XX, 2006. The abuse of volatile organic solvents (inhalants) leads to diverse sequelae at levels ranging from the cell to the whole organism. This paper reviews findings from the last 10 years of animal models investigating the behavioral and mechanistic effects of solvent abuse. In research with animal models of inhalant abuse, NMDA, GABA A , glycine, nicotine, and 5HT 3 receptors appear to be important targets of action for several abused solvents with emerging evidence suggesting that other receptor subtypes and nerve membrane ion channels may be involved as well. The behavioral effects vary in magnitude and duration among the solvents investigated. The behavioral effects of acute and chronic inhalant abuse include motor impairment, alterations in spontaneous motor activity, anticonvulsant effects, anxiolytic effects, sensory effects, and effects on learning, memory and operant behavior (e.g., response rates and discriminative stimulus effects). In addition, repeated exposure to these solvents may produce tolerance, dependence and/or sensitization to these effects. © 2006 Elsevier Inc. All rights reserved. Keywords: Volatile organic solvents; Inhalants; Toluene; Behavior; Animal models; Mechanisms of action Contents 1. Introduction .............................................................. 637 2. Animal models ............................................................ 638 3. Cellular mechanisms of action..................................................... 638 3.1. Effects on NMDA and non-NMDA receptors ......................................... 638 3.2. Effects on GABA A , glycine and 5HT 3 receptors ........................................ 639 3.3. Effects on nicotinic acetylcholine receptors (nAChRs) ..................................... 639 3.4. Effects on voltage-gated ion channels ............................................. 640 3.5. Effects on dopamine system .................................................. 640 3.6. Effects on other molecular targets ............................................... 640 4. Behavioral effects ........................................................... 641 4.1. Motor function ......................................................... 641 4.2. Anticonvulsant and convulsant effects ............................................. 641 Neurotoxicology and Teratology 28 (2006) 636 – 647 www.elsevier.com/locate/neutera ☆ Supported in part by NIDA grants R01DA15095 and R01DA015951 to SEB and grant 43604-M to SLC from Conacyt, Mexico. ⁎ Corresponding authors. Bowen is to be contacted at Departmentof Psychology, WayneState University, 5057 Woodward Ave., Detroit MI 48202, USA. Tel.: +1 313 577 9546; fax: +1 313 577 7636. Cruz, Tel.: +52 55 5061 2853; fax: +52 55 5061 2863. E-mail addresses: Scott.Bowen@wayne.edu (S.E. Bowen), slcruz@cinvestav.com (S.L. Cruz). 1 Dr. Bowen and Dr. Cruz contributed equally to this review. 0892-0362/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ntt.2006.09.005