ADMINISTRATION OF THYROTROPIN RELEASING HORMONE (TRH) TO RATS RELEASES DOPAMINE IN N-ACCUMBENS BUT NOT N-CAUDATUS

Bilateral injection of thyrotropin releasing hormone (TRH; 10 μg) into the n. accumbens of rats produced a short-lasting increase in co-ordinated locomotor activity and behavioural changes similar to those produced by injection of dopamine at this site. These effects were potentiated and prolonged by pretreatment with tranylcypromine (5 mg/kg i.p.). Injection of haloperidol (2.5 μg bilaterally) into the n. accumbens blocked the behavioural changes produced by intra-accumbens injection of TRH (10 μg bilaterally. 30min after tranylcypromine 5 mg/kg i.p.). Destruction of the presynaptic dopamine terminals with 6-hydroxydopamine (8 μg bilaterally) abolished the effects of intra-accumbens injection of TRH (10 μg bilaterally) in either untreated or tranylcypromine pretreated rats. This inhibition was not due to non-specific damage to post-synaptic dopamine receptors since these rats showed a normal locomotor response to intra-accumbens injection of dopamine (5 μg bilaterally. 30min after tranylcypromine 5 mg/kg). These results suggest that TRH is acting by release of dopamine. Peripheral injection of TRH (20 mg/kg) produced behavioural changes similar to those observed after central administration of this drug. Although these effects were not enhanced by pretreatment with tranylcypromine (5 mg/kg. 30min before TRH), they were blocked by peripheral injection of haloperidol (1 mg/kg). Injection of thyroid stimulating hormone (TSH: 20 mg/kg i.p.) produced no behavioural changes suggesting that peripherally injected TRH is not acting by release of TSH. Injection of TRH (20 mg/kg i.p.) to unilateral nigro-striatal lesioned rats failed to induce circling. Furthermore pretreatment with TRH (2 mg/kg i.p.) did not enhance the turning produced by methamphetamine (0.5 mg/kg) 3 hr later in tranylcypromine-treated animals. This evidence suggests that in contrast to its effects in the n. accumbens TRH is unable to release dopamine in the n. caudatus. © 1979.