RESUMEN
To determine the functional presence of dopamine (DA) autoreceptors on tuberoinfundibular dopamine (TIDA)-ergic neurons in awake rats, a microdialysis probe was implanted into the mediobasal hypothalamus (MBH). In the presence of the re-uptake inhibitor nomifensine, which increased DA levels to 350% of basal values, systemic administration of the non-selective D1/D2 antagonist haloperiol induced an immediate increase in DA and DOPAC levels to 145% of pretreatment values. However, neither local infusion of the selective D2 antagonist sulpiride nor of the D1 antagonist SCH 23390 affected the nomifensine-elevated extracellular DA or DOPAC levels in the MBH. Systemic administration of the D2 antagonist raclopride equally did not affect the nomifensine-elevated DA release in the MBH. Upon basal extracellular DA levels (without nomifensine), local infusion of the D2 agonist (-)N-0437 equally did not affect the DA or DOPAC levels in the MBH. Furthermore, the increase in DA levels induced by haloperidol could not be antagonized by the D1 agonist CY 208-243. Therefore, the present study does not provide support for the concept of functional autoreceptors located on TIDA neurons regulating the release of DA. Possibly, the effect of haloperidol was non-DA-ergic in character.
Asunto(s)
Hipotálamo Medio/química , Receptores Dopaminérgicos/análisis , Ácido 3,4-Dihidroxifenilacético/análisis , Animales , Benzazepinas/farmacología , Estado de Conciencia , Antagonistas de Dopamina/farmacología , Haloperidol/farmacología , Masculino , Microdiálisis , Nomifensina/farmacología , Racloprida , Ratas , Ratas Wistar , Salicilamidas/farmacología , Sulpirida/farmacologíaRESUMEN
The TIDA neurons, which constitute part of the arcuate nucleus-ME complex, play an important inhibitory role in the regulation of the PRL secretion from the adenohypophysis. To simultaneously study the release of DA from the TIDA neurons and the PRL secretion from the adenohypophysis in awake rats, a microdialysis probe was implanted into the MBH together with a permanent heartcannula in male rats. The extracellular levels of DA in the MBH as measured by microdialysis decreased to 25% of basal values after local infusion of TTX (1 mumol/l), indicating that the released DA was directly derived from neuronal activity. DOPAC levels were not affected. This local infusion of TTX into the MBH induced parallel to the immediate decrease in DA levels, a profound increase in PRL concentration in the blood (from 10 to 55 ng/PRL-RP-2/ml) directly after infusion. Thus, the area in which the dialysis probe was inserted indeed included the DA-ergic neurons that regulate the PRL secretion. Evidence for a functional re-uptake system in the MBH was obtained by local infusion of the re-uptake inhibitor nomifensine (5 mumol/l) which induced an increase in DA release to 350% of basal values, without affecting the DOPAC levels. In spite of this increase in DA levels, the PRL concentration in the blood was not affected. In pseudopregnant female rats, relatively high levels of extracellular DA in the MBH were obtained during the interphase during which the PRL levels are low, while lower DA levels were apparent during the phase the spontaneous nocturnal PRL surge normally appears. Taken together, the approach presented in this study, i.e. the simultaneous measurements of DA in the MBH and PRL in the blood, establishes an advanced method enabling studies on the DA-PRL interactions in awake animals.