Ontogeny of GABA-ergic and dopaminergic mediation of gnawing behavior in the mouse

Abstract

The ontogenetic course of dopaminergically mediated gnawing and the potentiation of this behavior by muscimol (a GABA receptor agonist) was explored in developing and young adult mice using a time-sampling (in 5-, 8-, 11-, and 14-day-old pups), or a corrugated paper procedure (in 14-, 17-, 20-, 23-, 26-, 35-, and 53-day-old animals). In experiment 1, the older mice group (14–53 days), displayed a dose-dependent gnawing behavior after methylphenidate, a dopamine indirect agonist (20, 30, 50 mg/kg). Similarly, in 5-, 8-, 11-, and 14-day-old pups, methylphenidate (10, 20, 50 mg/kg) evoked stereotyped gnawing (or indissociable gnawing-licking in 5-day-old pups), with maximal effects after the two lower doses at 8–11 days of age (experiment 2). Muscimol pretreatment (dosages ranging from 0.025 to 1.3 mg/kg) induced a clear-cut potentiation of gnawing elicited by methylphenidate (10 or 20 mg/kg) as early as 8 days of age (experiments 3 and 4). However, muscimol did not potentiate gnawing in 5-day-old pups treated with 10 or 2.5 mg/kg methylphenidate. The effectiveness of methylphenidate in inducing gnawing-licking among 5-day-old pups confirms the early maturation of central dopamine receptors reported in the literature. It is speculated that the absence of potentiating action of muscimol on methylphenidate-induced gnawing-licking at this age may be due to a functional immaturity of the GABAergic striato-nigro-tectal system, which is thought to transmit dopaminergic striatal stereotyped response at the output stations (recent review by Scheel-Krüger 1986). It is also pointed out that the lack of behavioral response in muscimol-methylphenidate treated neonates may indicate that their motor repertoire has not yet sufficiently differentiated.