Chronic intermittent toluene inhalation in adolescent rats alters behavioural responses to amphetamine and MK801

Abstract

Abuse of toluene-containing inhalants is common during adolescence, with ongoing chronic misuse associated with adverse outcomes and increased risk for addictive behaviours in adulthood. However, the mechanisms mediating the adaptive processes related to these outcomes are not well defined. To model human abuse patterns we exposed male adolescent Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (CIT, 10,000 ppm) or air (control) for 1h/day, three times/week for 3 weeks. The effects of CIT on behaviour and recovery were monitored. Locomotor activity was recorded following two consecutive injections of amphetamine (1mg/kg, i.p.) 72 and 96 h after the last exposure. This was followed with injection of the NMDA receptor antagonist MK801 (0.5mg/kg, i.p.) 20 days after the last exposure. CIT resulted in a significant and persistent retardation in weight gain during the exposure period and abstinence (p<0.05). Repeated exposure resulted in tolerance to the onset of toluene-induced behaviours and recovery latency. There was a reduction in the acute stimulant effects of amphetamine in CIT-exposed animals and an increase in the magnitude of locomotor activity (p<0.0125) following a subsequent exposure when compared to the responses observed in controls; this was associated with altered locomotor responses to MK801. Repeated exposure to CIT during adolescence alters parameters of growth, as measured by body weight, and leads to tolerance, indicating that increasing concentrations of the compound may be needed to reach the same behavioural state. Toluene during this period also alters responses to a psychostimulant which may be related to long-term glutamatergic dysfunction.