Different sensitivity to ethanol in alcohol-preferring sP and -nonpreferring sNP rats.
OBJECTIVE
Clinical research has proposed that initial sensitivity to ethanol may be negatively correlated with levels of subsequent ethanol intake; consistently, alcohol-preferring P rats were found to be less sensitive to the ataxic and sedative/hypnotic effects of ethanol than -nonpreferring NP rats. The present study investigated the initial sensitivity to the ataxic and sedative/hypnotic effects of ethanol and to the sedative/hypnotic effects of pentobarbital and diazepam in selectively bred Sardinian alcohol-preferring sP and -nonpreferring sNP rats.


METHODS
In experiment 1, time to lose (onset) and regain (sleep time) the righting reflex after the acute intraperitoneal (ip) administration of 3.0 and 3.5 g/kg ethanol were measured in sP and sNP rats. In experiment 2, sP and sNP rats were required to perform a motor coordination task on a Rota-Rod after the acute intragastric administration of 2.0, 2.5, and 3.0 g/kg ethanol. Experiment 3 assessed onset and sleep time in sP and sNP rats after the acute injection of pentobarbital (40 mg/kg; ip) and diazepam (15 and 20 mg/kg; ip).


RESULTS
In experiment 1, sP rats took shorter times to lose the righting reflex and regained this reflex over longer periods of time and at lower blood ethanol levels than sNP rats. In experiment 2, ethanol affected motor coordination to a greater extent in sP than sNP rats. In contrast, results from experiment 3 showed that sP and sNP rats were not differentially sensitive to the sedative/hypnotic effects of pentobarbital and diazepam.


CONCLUSIONS
The results of experiments 1 and 2 suggest that sP rats possess a genetically determined, greater sensitivity to the motor impairing and sedative/hypnotic effects of ethanol than sNP rats. Although caution should be adopted before hypothesizing any comparison to humans, these results may feature sP rats as an experimental model of those subsets of human alcoholics with initial high sensitivity to ethanol challenges. Finally, the results of experiment 3 suggest a minimal involvement of the benzodiazepine and barbiturate recognition sites in the differential sensitivity to ethanol of sP and sNP rats.
Colombo
G
G
CNR Center for Neuropharmacology, Cagliari, Italy. colomb@unica.it
Agabio
R
R
Carai
M A
MA
Lobina
C
C
Pani
M
M
Reali
R
R
Vacca
G
G
Gessa
G L
GL
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
D002492:Central Nervous System Depressants; D018757:GABA Modulators; D011963:Receptors, GABA-A; D000431:Ethanol; D010424:Pentobarbital; D003975:Diazepam