Mw. West et al., Calcium channel agonist (-)-BAY k 8644 suppresses free and limited access intake of alcohol in genetic drinking rats, PSYCHOPHAR, 142(3), 1999, pp. 261-269
Drugs which possess selective actions on a given voltage operated calcium (
Ca2+) channel (VOCC) are reportedly involved in the pharmacological actions
of alcohol. Recently it was shown that the I,4-dihydropyridine (-)-BAY k 8
644, an L-type VOCC agonist, reduces alcohol intake relatively selectively
in the genetic drinking AA rat. This study determined whether (-)-BAY k 864
4 would alter volitional alcohol drinking in two other genetic models of al
coholism, male P rats and anew strain of male and female high ethanol prefe
rring (HEP) rats. By use of a standard 10-day preference test for water ver
sus 3 to 30% alcohol, the maximally preferred concentration of alcohol was
first determined for each rat individually, i.e. 9%, 13% or 15%. Then the r
ats were allowed free access over 24 h or limited access to alcohol for onl
y 2 h, during which time the intakes of water and preferred solution of alc
ohol were recorded. After the drinking patterns stabilized for 4 days, sali
ne, a solutol vehicle solution or (-)-BAY k 8644 was administered: (1) in a
dose of 0.125, 0.25 or 0.5 mg/kg given intraperitoneally twice daily for 4
days during free access to alcohol; and (2) for 3 days in a dose of 0.125
or 0.25 mg/kg given subcutaneously 30 min prior to 2 h of limited access to
alcohol. Fluid intakes were recorded for either 4 or 8 days after limited
and free access conditions, respectively. Whereas the control solutions wer
e without effect during 24 h access, (-)BAY k 8644 caused a significant dos
e-dependent suppression of up to 80% in absolute g/kg and proportion of alc
ohol to total fluid consumed; this decline persisted in the post drug perio
d. During the limited access paradigm, (-)-BAY k 8644 similarly reduced alc
ohol drinking maximally within the first 15 min of presentation of alcohol;
again, this reduction persisted over the remaining 105 min of alcohol acce
ss. Also, individual levels of blood alcohol declined concurrently with the
suppression of drinking. These results demonstrate that (-)-BAY k 8644 pos
sesses a short latency of action on alcohol intake and that its salutary ef
fects on drinking persist after the drug is terminated. Finally, the hypoth
esis that L-type calcium channel agonists may be useful as a therapeutic ad
junct in the treatment of alcoholism is extended.