Differential effects of inhaled toluene on locomotor activity in adolescent and adult rats

Abstract

Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm "air" controls at both ages. These changes depended upon when activity was measured - during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the "recovery" period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen prevalence of inhalant abuse.

Figure 1

Schematic of toluene exposures and locomotor activity testing for each of the 12 days of toluene exposures. Solid boxes indicate toluene exposure and concurrent locomotor activity monitoring. Open boxes indicate a “recovery period” monitoring spontaneous locomotor activity in a toluene-free environment for 30 min immediately following the final toluene exposure each day. Total cumulative exposure time each day – at 30 min – is equivalent among the three exposure patterns, “Standard,” “Rapid” or “Paced.”

Figure 2

Effects of inhaled 0, 8,000 ppm, or 16,000 ppm toluene during exposures (left side) on rat locomotor activity, and in the “recovery” period following exposure (right side) expressed as percent of 0-ppm air control. In the top panel, mean (± s.e.m.) total distance traveled during a “Standard” exposure pattern summed across two 15-min sessions (separated by a 120-min interval); in the middle panel, mean (±s.e.m.) total distance traveled during a “Rapid” exposure pattern summed across two 15-min sessions (30-min interval); in the bottom panel, mean (± s.e.m.) total distance traveled during a “Paced” exposure summed across six 5-min sessions (with 30-min intervals). Mean (± s.e.m.) total distance traveled in a 30-min post-exposure “recovery” period is similarly expressed as percent of 0-ppm air control in all three panels. * Significantly different from 0 ppm (p≤ 0.05). # Significantly different across age (p≤ 0.05). N=8 rats per concentration.

Figure 3. Standard Exposure Pattern

Effects of inhaled 0, 8,000 ppm, or 16,000 ppm toluene exposures (top panel) on rat locomotor activity, and post-exposure (bottom panel). Mean (±s.e.m.) total distance traveled during exposure (top panel) summed across two 15-min sessions (with a 120-min interval) is expressed as percent of 0-ppm air control. Mean (±s.e.m.) total distance traveled in a 30-min post-exposure session (bottom panel) is similarly expressed as percent of 0-ppm air control. * 8,000 ppm significantly different from 0 ppm (p≤ 0.05). # 16,000 ppm significantly different from 0 ppm (p≤ 0.05). N=8 rats per concentration.

Figure 4. Rapid Exposure Pattern

Effects of inhaled 0, 8,000 ppm, or 16,000 ppm toluene exposures (top panel) on rat locomotor activity, and post-exposure (bottom panel). Mean (±s.e.m.) total distance traveled during exposure (top panel) summed across two 15-min sessions (with a 30-min interval) is expressed as percent of 0-ppm air control. Mean (±s.e.m.) total distance traveled in a 30-min post-exposure session (bottom panel) is similarly expressed as percent of 0-ppm air control. * 8,000 ppm significantly different from 0 ppm (p≤ 0.05). # 16,000 ppm significantly different from 0 ppm (p≤ 0.05). N=8 rats per concentration.

Figure 5. Paced Exposure Pattern

Effects of inhaled 0, 8,000 ppm, or 16,000 ppm toluene exposures (top panel) on rat locomotor activity, and post-exposure (bottom panel). Mean (±s.e.m.) total distance traveled during exposure (top panel) summed across six 5-min sessions (with 30-min inter-exposure intervals) is expressed as percent of 0-ppm air control. Mean (±s.e.m.) total distance traveled in a 30-min post-exposure session (bottom panel) is similarly expressed as percent of 0-ppm air control. * 8,000 ppm significantly different from 0 ppm (p≤ 0.05). # 16,000 ppm significantly different from 0 ppm (p≤ 0.05). N=8 rats per concentration.