Semicircadian Rhythm of Dopamine Release in the Mediobasal Hypothalamus in Awake Rats during Pseudopregnancy: Evidence that a Thyrotropin-Releasing Hormone Analogue Stimulates Dopamine Release and thereby Inhibits Prolactin Secretion

Abstract

The release of dopamine (DA) from tuberoinfundibular (TIDA) neurons during prolactin (PRL) surge and nonsurge periods and the effects of the thyrotropin-releasing hormone (TRH) analogue CG 3703 on DA and PRL secretion were studied in awake pseudopregnant (PSP) rats by simultaneous measurement of extracellular DA levels in the mediobasal hypothalamus (MBH) by means of microdialysis and of plasma PRL concentrations by radioimmunoassay of PRL in blood sampled from a permanent heart cannula. Since basal DA levels were low, the experiments were performed under local infusion of the reuptake inhibitor nomifensine (5 µmol/l), which increased extracellular DA levels 5-fold around the probe, but did not affect the occurrence of the nocturnal PRL surge on day 7–8 of PSP. Under nomifensine conditions, during the interphase (18.00–1.00 h), plasma PRL levels were low (<50 ng/ml), while the DA release from TIDA neurons was elevated (∼250%) relative to the DA values measured during the phase when the nocturnal PRL surge occurred (100%; 1.00–12.00 h; plasma PRL levels were elevated to ∼300 ng/ml). Thus, semicircadian rhythms were detected both for DA and PRL, which were broadly reciprocal in timing. The TRH analogue CG 3703 (100 and 500 µg/ animal i.v.), when administered at 00.00 h, dose-dependently increased extracellular DA levels (to 300 and 500% of pretreatment values, respectively) and postponed the PRL surge in a corresponding manner (for ∼2 and 3 h, respectively). Thus, in addition to its PRL-releasing effects, TRH can also suppress the PRL secretion by stimulating the release of DA from TIDA neurons, thereby increasing the inhibitory DAergic tone on lactotrophs. During the interphase, when DA levels were relatively elevated, administration of the DA blocking agent HA 966 (100 mg/kg body weight i.p.) at 20.00 h resulted in a short-lasting decrease in extracellular DA levels (to ∼60% of pretreatment values for 30 min) accompanied by an immediate, short-lasting increase in PRL levels (to 400 ng/ml for ∼1 h). Administration of CG 3703 (500 µg/ animal i.v.) in combination with HA 966 (100 mg/kg body weight i.p.) at 20.00 h prevented the decrease in DA levels and the rise in plasma PRL values. Thus, the TRH analogue and HA 966 counteracted each other regarding the DAergic system, which again illustrates the stimulatory effect of the TRH analogue on the release of DA from TIDA neurons. Moreover, our results suggest that the interphase and the phase during which the nocturnal PRL surge occurs under the condition of PSP differ with regard to the DAergic inhibition of the PRL secretion; during the interphase the DAergic inhibitory tone prevents the rise in PRL secretion, while during the nocturnal PRL surge period another factor in addition to a decrease in DA levels appears necessary to increase plasma PRL levels.

Neuronal Dopamine Subpopulations Maintained in Hypothalamic Slice Explant Cultures Exhibit Distinct Tyrosine Hydroxylase mRNA Turnover Rates

“…These characteristics would be important in a neuronal population that is activated for hourly intervals and then rapidly adjusts activity in response to afferents and /or feedback regulation. In support of this contention, arcuate DA neurons were recently shown to display a semicircadian rhythm in pseudopregnant rats (Timmerman et al, 1995). Fos-related activity, an indicator of neuronal activation, peaked twice daily in arcuate DA neurons in 3-6 hr and subsided to baseline levels within 4 -6 hr (Lerant et al, 1996).…”

Exposição perinatal de ratos ao glifosato (roundup®): efeitos sobre o comportamento materno e sobre o desenvolvimento físico e neurocomportamental da prole desde o nascimento até a idade adulta

“…Em fêmeas a forma de ataque a um intruso difere da apresentada por machos dominantes em seu território (BLANCHARD et al, 1984); as fêmeas apresentam ataques laterais, investigação com o focinho (farejar) e pequenas mordidas, comportamento que não é visto em machos dominantes contra intrusos (LEYHAUSEN, 1973). As fêmeas também podem apresentar agressividade contra outras fêmeas, porém muito menos feroz do que a demonstrada contra um macho intruso (PARMIGIANI et al,1988 A DA atua no controle tônico da síntese e secreção de prolactina; a atividade rítmica semi-circadiana dos neurônios dopaminérgicos do sistema túberoinfundibular determina os picos diurno e noturno de secreção de prolactina (TIMMERMAN et al, 1995). Esta, por sua vez, desempenha um papel importante na estimulação do cuidado materno, bem como participa da manutenção deste comportamento RUSSELL, 1981;BRIDGES et al,1997).…”