Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene

Abstract

Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. While studies have assessed outcomes of exposure to inhalants in adult male animals, there is little research on the neurobehavioral effects of inhalants in female or younger animals. In attempt to address these shortcomings, we exposed male and female Long-Evans rats to 20 min of 0, 2,000, 4,000, or 8,000 parts per million (ppm) inhaled toluene for 10 days in rats aged postnatal (PN) day 28-39 (adolescent), PN44-PN55, or >PN70 (adult). Animals were observed individually in 29-l transparent glass cylindrical jars equipped with standard photocells that were used to measure locomotor activity. Toluene significantly increased activity as compared to air exposure in all groups of male and female rats with the magnitude of locomotor stimulation produced by 4000 ppm toluene being significantly greater for female adults than during any age of adolescence. The results demonstrate that exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous locomotor behavior in rats and that the expression of these effects appears to depend upon the postnatal age of testing and sex of the animal.

Effect of Chronic Inhalation of Toluene on Behavior of Rats of Various Age Groups in Multi-Branched Maze

“…In this study, we demonstrated that the toluene effect also depended on animal age. The age-dependence of the toxic effects was also demonstrated in our previous studies [6,7] and in some other reports [2]. We previously showed more rapid motor learning in young rats after chronic toluene inhalation in comparison with adult animals [6].…”

“…The effect of chronic toluene inhalation largely depends on toxicant dose and animal sex [2,4]. In this study, we demonstrated that the toluene effect also depended on animal age.…”

“…Cell sites and mechanisms mediating these disturbances are still unknown, but the infl uence of toluene on dopamine-, GABA-, serotonin-, and cholinergic neurons is thought to play a role [9,10]. There are data that chronic inhalation of toluene produces a negative effect on memory and learning [3,4] and this effect depends, among other factors, on age [2,4].…”

Reproductive Toxicology and Teratology of Abused Toluene

“…Taken together, these results imply that abuse of organic solvents during pregnancy in humans may result in greater risks to fetuses and neonates than continuous exposures at lower concentrations. It is important to note that developmental shifts in sensitivity to the negative consequences of binge organic solvent exposures extend into early postnatal life, in both neonatal models of third-trimester exposures and -although not within the scope of this reviewinto adolescence, a period of enhanced risk for toluene abuse (cf., [Bowen et al 2007a]). Prenatal exposure to toluene produces significant doseresponse shifts in psychopharmacological responses that may be indicative of neural mechanisms for the neurobehavioral disturbance associated with fetal solvent syndrome.…”

Long-Term Behavioral Consequences of Prenatal Binge Toluene Exposure in Adolescent Rats

“…Only a handful of studies have examined gross dysmorphology following patterns of prenatal toluene exposure that mimic inhalant abuse (i.e., repeated, high dose short exposures) [8,10,12,26,59]. In previous work examining prenatal binge toluene exposure, repeated 15 min (8,000 or 12,000 ppm) exposure twice a day (30 min total per day) from Gestation Day 8 (GD8) through GD20 produced significant increases in total minor and gross malformations, including reduced body weight, soft tissue anomalies (e.g., missing eyes), and skeletal abnormalities (shortened and/or missing digits and missing limbs, reduced skeletal ossification), "runting" and fetal or postnatal death [8,51].…”