The effect of systemically administrated cholecystokinin analog, caerulein, on monoaminergic neurons was examined in discrete regions of rat brain. A single injection of caerulein (400 micrograms/kg, i.p.) significantly elevated 5-hydroxyindoleacetic acid (5HIAA) levels in the prefrontal cortex lateral field, nucleus accumbens, tuberculum olfactorium and striatum after 2 hours, together with a significant increase in striatal serotonin (5HT). Moreover, the time-course study showed that the caerulein-induced increase in both 5HIAA and 5HT levels lasted even for 24 hours, and their levels tended to recover to the control values gradually. This time-dependent change was not found in the other monoamines and their metabolites. These results suggest a long-lasting action of caerulein on 5HT neurons in specific regions of rat brain.

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PubMedDate not supplied

Effect of DN-1417, a thyrotropin releasing hormone analog, on dopaminergic neurons in rat brain.

Acute and chronic effects of gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.

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