GABA agonists dissociate striatal unit activity from drug-induced stereotyped behaviour

Dexamphetamine and apomorphine produced behavioural activation and stereotypy accompanied by increased neuronal activity in the striatum in freely moving rats. The GABA agonist muscimol (0.5–2.0 mg/kg i.p.) produced dose-related inhibition in the striatum. Muscimol pretreatment blocked the striatal activation produced by dexamphetamine and apomorphine, but significantly enhanced drug-induced stereotypy. Similarly, aminooxyacetic acid (25 mg/kg i.p. daily for 4 days) elevated whole-brain GABA levels 2-fold, converted the striatal response to apomorphine and dexamphetamine from activation to inhibition, and enhanced drug-induced stereotypy. It is concluded that (1) enhanced activity at GABA-ergic synapses may either increase impulse traffic in inhibitory afferents to the striatum, decrease impulse traffic in excitatory afferents to the striatum, or both, and (2) since muscimol potentiated stereotypy at the same time abolishing striatal activation normally accompanying drug-induced stereotypy, it is clear that activation of striatal neurones is not an essential component of stereotypy. Furthermore, it is unlikely that the striatum is the primary site of drug action for the induction of stereotypy.