Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone analog, on in vivo dopamine release and turnover in rat brain

Abstract

Effects of taltirelin hydrate (CAS 103300-74-9, TA-0910), a novel thyrotropin-releasing hormone (TRH) analog, on the cerebral monoamine systems, especially the release and turnover of dopamine (DA) in rat brain were compared with those of TRH by intraperitoneal administration. Taltirelin hydrate (1-10 mg/kg) increased the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and corpus striatum for 3 h in a microdialysis study. TRH (30 mg/kg) also increased the levels of these substances, the potency of TRH being the same as that of taltirelin hydrate at doses of 1-3 mg/kg. Taltirelin hydrate (10 mg/kg) also caused an increase in 3-methoxytyramine (3-MT: DA metabolite) until 6 h after the treatment and L-3-dihydroxyphenylalanine (DOPA: precursor of DA and noradrenaline). Taltirelin hydrate also increased the 3-methoxy-4-hydroxyphenylglycol (MHPG: noradrenaline metabolite) level in the frontal cortex and hypothalamus, and 5-hydroxytryptophan (5-HTP: serotonin precursor) accumulation and 5-hydroxyindoleacetic acid (5-HIAA: serotonin metabolite) level in the nucleus accumbens or corpus striatum. These results suggest that taltirelin hydrate possesses not only an enhancing effect on DA release, but also a stimulating effect on the monoamine system. Moreover, these actions were 10-30 times stronger and also longer-lasting than those of TRH. In addition, the mechanisms of DA release induced by these drugs were different from those induced by methamphetamine.