Psychopharmacology (2006) 186: 159–167 DOI 10.1007/s00213-006-0359-6 ORIGINAL INVESTIGATION Wynne K. Schiffer . Dianne E. Lee . David L. Alexoff . Rich Ferrieri . Jonathan D. Brodie . Stephen L. Dewey Metabolic correlates of toluene abuse: decline and recovery of function in adolescent animals Received: 21 September 2005 / Accepted: 21 February 2006 / Published online: 22 April 2006 # Springer-Verlag 2006 Abstract Rationale: Children and adolescents will read- ily abuse household products that contain solvents such as toluene. It is likely that reinforcing exposures to toluene alter brain glucose metabolism. Objective: Using an animal model of drug reinforcement, we sought to identify a metabolic signature of toluene abuse in the adolescent rodent brain. Small animal PET (microPET), in combina- tion with the glucose analog radiotracer, 18 FDG, were used to evaluate the metabolic consequences of inhaled toluene. Methods: The exposure protocol paralleled our previously established method for assessing the conditioned reinforc- ing effects of toluene (5,000 ppm) using the conditioned place preference (CPP) paradigm. Animals were scanned at baseline and 2 h after the last exposure. Follow-up 18 FDG scans occurred 1 day, 3 weeks, and 2 months later. Results: After six pairings, 38% of the animals preferred the toluene paired chamber and 25% were averse. The immediate metabolic effect in toluene-exposed animals was a 20% decline in whole brain 18 FDG uptake. Twenty-four hours following the last exposure, the whole brain decline was 40%, and 2 months later, the decline was 30% of pretoluene levels. A region-by-region analysis demonstrated signifi- cant additional decreases in the pons, cerebellum, striatum, midbrain, temporal cortex, and hippocampus. Two months after toluene cessation, regions of complete metabolic recovery were the thalamus and cerebellum; however, the temporal cortex did not recover. Conclusions: Brain uptake of 18 FDG appears to be a useful tool for examining the metabolic impact of toluene abuse, which include a profound decline followed by region-specific recovery after cessation. Keywords Abuse . Brain imaging . PET . Deoxyglucose . Animal model . Inhalant abuse Introduction There is a growing concern that solvent abuse may result in irreversible structural damage to the nervous system which manifest as changes in behavior and neurological function (for review, see Filley et al. 2004). In fact, for abused solvents with demonstrated toxicity, the type of neurolog- ical damage may be closely related to the structure of the compound, while the degree of impairment and the extent of reversibility are most likely related to factors such as the exposure concentration, and the number or duration of each exposure (Spencer and Schaumburg 1985). These param- eters also impact the salience of inhaled solvents in an animal model of toluene abuse (Gerasimov et al. 2003). This becomes especially critical because the primary abusing population of these inhalants are children between the ages of 12 and 16, and because members of this vulnerable population are 46 times more likely to become injection drug abusers (Schutz et al. 1994). The pivotal biological role of the central nervous system (CNS) in healthy development and its susceptibility to toluene underline the urgent need for further clinical and experi- mental research in both adolescent and adult animals. Toluene, in particular, precipitates an organic mental syndrome characterized by personality change and in- tellectual decline with attendant mild dysfunction of the peripheral nervous system (PNS; Filley et al. 2004). Acute toluene intoxication produces a reversible syndrome characterized by encephalopathy and cerebellar ataxia, and toluene abusers who abstain from inhalant abuse show partial neurobehavioral recovery when toluene is no longer present (Hormes et al. 1986). Chronic inhalation abuse induces a more severe white matter leukoencephalopathy characterized by a profound reduction in brain white matter W. K. Schiffer . D. E. Lee . D. L. Alexoff . R. Ferrieri . S. L. Dewey Chemistry Department, Bldg #555, Brookhaven National Laboratory, Upton, NY 11973, USA W. K. Schiffer (*) . J. D. Brodie . S. L. Dewey Department of Psychiatry, NYU School of Medicine, New York, NY 10016, USA e-mail: wynne@bnl.gov Tel.: +1-631-3446269 Fax: +1-586-2796268