Page 92 - Pagetit

4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

Fig. 4.1 Fluorodeoxyglucose (FDG)-PET images of normal subject after
placebo (diet soda) and ethanol (0.75 g/kg)

80

Placebo

0
µmol/100g/min

Ethanol (0.75 gm/kg, p.o.)

Source: Wang et al., 2000. Reproduced with permission of the publisher.

Of particular clinical importance is the development of adaptive changes
in synaptic function in response to ethanol’s action on ion channels (see
Chapter 2), which also contribute to tolerance. Ethanol tolerance and
dependence may be explained, in part, by changes in the function of GABA(A)
receptors. Cross-tolerance and sensitization (see Chapter 3) have also been
intensely researched during the past few years. Sensitization to the
neuroactive steroids – endogenous modulators of the GABA-A receptors –
influences ethanol dependence and withdrawal and may explain gender
differences in the molecular effects of ethanol (Grobin et al., 1998). Animal
models of ethanol dependence have identified GABA-A receptor genes as
likely mediators of the behavioural adaptations associated with ethanol
dependence and withdrawal (Grobin et al., 1998).
A withdrawal syndrome that may be severe enough to be fatal
characterizes ethanol withdrawal. The severity of this syndrome is a function
of the amount of ethanol consumed, frequency of use, and the duration of
drinking history. Early signs of withdrawal are severe shaking, sweating,
weakness, agitation, headache, nausea and vomiting, and rapid heart rate.
Within 24 hours after stopping drinking, seizures may start to appear (Jacobs
& Fehr, 1987). The alcohol withdrawal can be complicated by the state that
is known as delirium tremens, and is characterized by severe agitation,
autonomic hyperactivity, hallucinations and delusions. Untreated, the

71

Chapter_4 71 19.1.2004, 11:42