Development of GABAergic modulation of mouse locomotor activity and pain sensitivity after prenatal benzodiazepine exposure.
Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. Locomotor activity (single 30-min session in a Varimex apparatus), hot-plate responding, and muscimol (GABAa agonist) effects thereon [see normative data in (16)] were assessed on postnatal day 14, 21, or 28. Prenatal oxazepam did not affect the development of hot-plate responding and muscimol analgesia; however, it reduced activity on day 14 (as in previous studies) and modified the profile of muscimol effects at 21 days (time of first appearance of an adult-like pattern of activity) and at 28 days. Specifically, oxazepam mice showed a faster recovery from the initial depression after 1 mg/kg of muscimol at the former age and a lack of rebound hyperactivity at the latter age. These effects might be explained either 1) by an accelerated development of GABAergic regulatory mechanisms, or 2) by the same monoaminergic system changes which can account for other effects of prenatal BDZ exposure (1,3). In any event, the dissociation phenomena found in the present study strengthen the notion that GABAergic influences contribute to the modulation of locomotor activity and of pain reactivity by mechanisms which are at least in part separate from each other (16).
Laviola
G
G
Section of Behavioural Pathophysiology, Istituto Superiore di Sanità, Roma, Italy.
Chiarotti
F
F
Alleva
E
E
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D010076:Oxazepam / Q000009:adverse effects*; D010146:Pain / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D010076:Oxazepam