Effects of ethanol, MK-801, and chlordiazepoxide on locomotor activity in different rat lines: dissociation of locomotor stimulation from ethanol preference.
Several lines of research have suggested a link between the reward value of a drug and its ability to stimulate locomotion. One goal of the present study was to determine whether ethanol preferentially stimulates locomotor activity in lines of rat that show a preference for ethanol. A secondary goal was to determine the extent to which the benzodiazepine-like and NMDA antagonistic action of ethanol accounted for its effect on locomotor activity. To meet these goals, the effects of varying doses of ethanol (0.125-1.0 g/kg), MK-801 (0.1-0.3 mg/kg), and chlordiazepoxide (0.3-3 mg/kg) on locomotor activity were studied in several lines of rats that had been habituated to the testing procedure. The effect of low doses of ethanol on motor activity in the Alcohol-Preferring (P) and Fawn-Hooded rats, which show a strong ethanol preference, were similar to those of the alcohol-nonpreferring (NP), Flinders Sensitive Line, and Flinders Resistant Line rats. Only the Flinder Resistant Line rats showed a small, but significant increase in locomotor activity after the administration of ethanol. The highest dose of ethanol (1.0 g/kg) produced locomotor depression in all lines except the P and NP lines, which were not tested at this dose. These findings do not support a link between locomotor stimulation by ethanol and ethanol preference. In contrast, all lines exhibited locomotor stimulation after moderate (0.1-0.3 mg/kg) doses of MK-801, but did not exhibit increases in activity following any dose of chlordiazepoxide. These data indicate that the profiles of activity after MK-801 and chlordiazepoxide were distinct from that of ethanol in the various rat lines.(ABSTRACT TRUNCATED AT 250 WORDS)
Criswell
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HE
Brain and Development Research Center, University of North Carolina School of Medicine, Chapel Hill 27599-7250.
Overstreet
D H
DH
Rezvani
A H
AH
Johnson
K B
KB
Simson
P E
PE
Knapp
D J
DJ
Moy
S S
SS
Breese
G R
GR
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013045:Species Specificity
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate; D002707:Chlordiazepoxide