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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

Other evidence of dopamine involvement following toluene inhalation
comes from studies on occupational toxicology. Subchronic inhalation
exposure to concentrations of toluene likely to be found in occupational
settings induces persistent changes in locomotor activity and the number of
dopamine D receptors in rat caudate (von Euler et al., 1993; Hillefors-
2
Berglund, Liu & von Euler, 1995). Toluene-induced locomotor hyperactivity
may be blocked by D receptor antagonists (Riegel & French, 1999).
2
Tolerance and withdrawal

The acute neurobehavioural effects of volatile solvents, including anxiolysis
and sedation, are those typically associated with central nervous system
depressants, and these effects may lead to continued use, tolerance and
withdrawal (Beckstead et al., 2000).
Tolerance may occur but it is considered difficult to estimate in humans.
It seems to be established after 1–2 months of repetitive exposure to volatile
solvents (American Psychiatric Association, 1994). Rats exposed to high
environmental concentrations of toluene vapours for long periods of time,
present tolerance to motor abnormalities (Himnan, 1984).
Withdrawal from volatile solvents in mice is characterized by increased
susceptibility to convulsions and may be reversed or diminished by other
solvent vapours, as well as by ethanol, midazolam and pentobarbital. These
data support the hypothesis that the basis for volatile solvent use may be its
ability to produce ethanol-like and depressant drug-like effects (Evans
&Balster, 1991).

Neurobiological adaptations to prolonged use
Persistent changes in dopamine receptor binding and function have been
found in rats exposed to low concentrations of toluene. In addition, acute
inhalation exposure to toluene is accompanied by an increase in extracellular
dopamine levels within the striatum (Stengard, Hoglund & Ungerstedt, 1994),
while prolonged exposure does not significantly change extracellular
dopamine levels in rat accumbens (Beyer et al., 2001).
Repeated exposure to toluene increased the acute motor-stimulant
response to cocaine and potentiated and prolonged cocaine-induced
increases in dopamine outflow in the nucleus accumbens, showing that
repeated exposure to toluene enhances behavioural and neurochemical
responses to subsequent cocaine administration in rats. This is evidence of
the development of sensitization and cross-sensitization, which are key
features in the development of dependence (see Chapter 3). These findings
suggest that exposure to toluene alters neuronal function in an area known
to be critically involved in substance dependence, by increasing sensitivity
to other psychoactive substances and may, therefore, increase the probability
of substance dependence (Beyer et al., 2001).

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