G. Wahlstrom, RECOVERY AFTER INTERRUPTED EXPOSURE DURING INDUCTION OF EXPERIMENTAL ALCOHOLISM IN THE RAT, Alcohol and alcoholism, 29(3), 1994, pp. 295-301
A model of alcoholism founded on a long-term treatment with intermitte
nt weekly ethanol exposures [each week a voluntary choice between 10%
(w/v) ethanol and water for 24 hr followed by an intraperitoneal (i.p.
) injection of 2.0 g/kg ethanol] was used to test the effect of a 10-w
eek interruption of the treatment. Three groups were tested. Group CT
had 65 weeks of treatment with no interruption. Group BT started the t
reatment at the same time as group CT, but no treatment was given in w
eeks 33-42. In group LS, the treatment started at the same time as it
was restarted in group BT (week 43). An evaluation period with a conti
nuous choice between ethanol and water was started in week 66. During
the evaluation period dependence, defined as a voluntary ethanol intak
e not influenced by changes in ethanol concentration, was determined b
y comparing the intake of a 10% (w/v) reference solution with that of
a 5% (w/v) test solution. At the start of the treatment the 24 hr volu
ntary ethanol intake in group CT and BT was inhibited maximally after
6-7 weeks of treatment. When group LS was started in week 43, a simila
r, but more marked, inhibition developed. In all groups, ethanol intak
e rose again after the inhibition. After restarting the treatment in g
roup BT, the rats could be divided into two subgroups. Group BT;LI wit
h a low intake of ethanol in week 32 had voluntary ethanol intake afte
r restarting the treatment which was similar to corresponding data rec
orded in group LS when starting the treatment. In group BT;HI with a h
igh intake of ethanol in week 32 there was no influence of the break i
n the treatment. The voluntary ethanol intake was similar to the corre
sponding intake in group CT and not to that seen in group LS. During t
he evaluation period, a marked dependence was recorded as a strong cor
relation between voluntary intake of ethanol as a 5 and a 10% solution
in group CT (r = 0.93; N = 11, P < 0.001). A similar dependence but w
ith a lower daily ethanol intake was recorded in group LS (r = 0.88, N
= 9, P < 0.01) after a treatment lasting for 22 instead of 65 weeks.
A dependence was recorded in group BT;HI (r = 0.97; N = 4, P < 0.05) b
ut not in group BT;LI (r = 0.63, N = 7, NS). Thus rats with a low inta
ke before the break of the treatment behaved as naive rats starting th
e treatment but did not show dependence, while rats with a high intake
before the break behaved in the same way as rats continuously exposed
to ethanol with regard to the development of dependence.