Effects of GABA analogues and their interactions with morphine on locomotor activity in two inbred strains of mice

DBA 2J (DBA) and C57BL6J (C57) display significant differences for their sensitivity to the effects of three GABA agonists (muscimol, THIP and SL 76002) on spontaneous locomotor activity. Particularly, these GABA agonists exhibit a biphasic response in locomotion of DBA mice, the lower dose eliciting an increase and the larger doses inducing a decrement of locomotion. Conversely, with the exception of THIP, the above reported GABA agonists cause only a reduction of locomotor activity in the C57 strain. Therefore, DBA mice seem to be more sensitive than C57 ones to the stimulant effect of GABA agonists on locomotoion. Piracetam, a compound structurally related to GABA, does not exhibit the biphasic dose-response curve obtained with muscimol, THIP and SL 76002 in DBA mice. When given in combination with morphine, muscimol, SL 76002 and piracetam do not modify the depressant effect induced by this opiate on locomotor activity of DBA mice; THIP, at the lowest dose used in the present study, antagonizes the decrease of locomotion elicited by morphine in this strain. Furthermore, muscimol, THIP, SL 76002 and piracetam antagonize morphine-induced hypermotility in C57 mice. The results are discussed with reference to the role that the strain of animals, the dosage and the time of testing have in the effects of GABA analogues as well as in their interactions with morphine on locomotor activity.