Novelty-associated locomotion: correlation with cortical and sub-cortical GABAA receptor binding

The present study was designed to determine whether variability in GABA (eta-aminobutyric acid)A receptor binding in cortical and subcortical brain regions was correlated with locomotor activity in a novel environment. Twenty four animals were rated for locomotor activity in a novel circular runway. Eight days later, locomotor activity was assessed following 1.5 mg/kg amphetamine sulfate (i.p.). After four to six days, animals were killed and samples were pooled in groups of four animals ranked according to novely locomotor score, and specific binding of the GABAA receptor antagonist [2-(3'-carboxy-2'-propyl)-3-amino-6-p-methoxy phenylpyridazinium bromide] ([3H]SR95531) was determined. Significant negative correlations were seen between specific ([3H]SR95531) binding and novelty induced locomotion in the cingulate and prefrontal cortices, and in the ventral pallidum. A near-significant negative correlation was seen in the striatum. Correlation coefficients between locomotion scores in the novel environment and specific [3H]SR95531 binding were: cingulate cortex, R = -0.91, P = 0.012; prefrontal cortex, R = -0.85, P = 0.032; ventral pallidum, R = -0.85, P = 0.030; striatum, R = -0.73, P = 0.097; and nucleus accumbens, R = -0.09, P = 0.85. The positive correlation between novelty- and amphetamine-induced locomotion was also quite high (R = 0.95, P = 0.004). These results are discussed in terms of their relevance to potential biochemical correlates of drug abuse vulnerability.