Tuberoinfundibular Dopaminergic Neuronal Activity Research Articles

A Sex Difference in the Stimulatory Afferent Regulation of Tuberoinfundibular Dopaminergic Neuronal Activity

The involvement of afferent neuronal systems in the maintenance of basal and prolactin-stimulated tuberoinfundibular dopaminergic (TIDA) neuronal activity was examined in female and male rats. The synthesis and turnover of dopamine (DA) was measured in the median eminence, the terminal region of the TIDA neurons, to estimate the activity of these neurons. Complete and retrochiasmatic deafferentations of the mediobasal hypothalamus were made 7 days prior to experimentation to either completely isolate the TIDA neurons from the rest of the brain or to interrupt neuronal connections from rostral brain regions to the TIDA neurons, respectively. Both complete and retrochiasmatic deafferentations decreased the basal rate of DA synthesis and turnover in the median eminence of female, but not of male rats. These results suggest that neuronal afferents originating rostral to the mediobasal hypothalamus stimulate TIDA neurons in the female but not in the male rat. Intracerebroventricular administration of rat prolactin increased DA synthesis in the median eminence of both sham and retrochiasmatic deafferentiated female and male rats showing that the stimulatory action of prolactin is not blocked by retrochiasmatic deafferentation. Ovariectomy reduced the rate of DA synthesis in the median eminence but retrochiasmatic deafferentation did not cause a further decrease in ovariectomized rats. These results suggest that retrochiasmatic deafferentation and ovariectomy may remove a stimulatory input to the TIDA neurons which is mediated through a common afferent neuronal pathway. These afferent influences do not appear to be operational in the adult male rat since retrochiasmatic deafferentation did not reverse the castration-induced increase in the rate of DA synthesis in the median eminence of male rats.

Activity of tuberoinfundibular dopaminergic neurons and concentrations of serum prolactin in the rat following lithium administration.

Maintenance of rats on a lithium-containing diet for 3-21 days resulted in a suppression of prolactin (PRL) secretion in vivo and in vitro. Lithium treatment also resulted in an increase in the activity of tuberoinfundibular dopaminergic neurons, as evidenced by an increased accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after inhibition of DOPA decarboxylase and an increased concentration of dopamine in the anterior pituitary gland. The accumulation of DOPA in the neurointermediate lobe of the pituitary gland, the prefrontal cortex, the striatum and the nucleus accumbens was also enhanced by lithium treatment. It is concluded that lithium treatment enhances the synthesis of dopamine in many brain regions and that an increased activity of tuberoinfundibular dopaminergic neurons results in an enhanced inhibitory control of PRL secretion.

The anterior hypothalamus provides stimulatory input to tuberoinfundibular dopamine neurons which is not mediated by prolactin.

Complete or retrochiasmatic deafferentations of the mediobasal hypothalamus were made in female rats 7 days prior to experimentation in order to determine the role played by putative afferent neuronal connections (1) in maintaining the basal neuronal activity of tuberoinfundibular dopaminergic (TIDA) neurons, and (2) in the stimulatory actions of prolactin on these neurons. The neuronal activity of TIDA neurons was estimated by measuring the rates of synthesis, turnover or metabolism of dopamine (DA) in the terminals of these neurons in the median eminence. Complete deafferentation of the mediobasal hypothalamus reduced the basal rate of DA synthesis, and retrochiasmatic deafferentation decreased the rates of synthesis, turnover and metabolism of DA in the median eminence. A knife cut 1 mm rostral to the retrochiasmatic cut failed to alter basal TIDA neuronal activity. These results suggest that afferent neuronal inputs originating in or coursing through the caudal portion of the anterior hypothalamus mediate a tonic stimulatory influence on TIDA neurons in the female rat. Intracerebroventricular administration of rat prolactin or systemic administration of haloperidol (which increases circulating levels of prolactin) increased DA synthesis in the median eminence of both sham-operated rats and retrochiasmatic-deafferentated rats. Thus, the stimulatory action of prolactin was not blocked by retrochiasmatic deafferentation. In addition, elimination of the basal stimulatory action of endogenous prolactin by pretreating animals with bromocriptine reduced the rate of DA synthesis in the median eminence of both sham- and retrochiasmatic-deafferentated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of electrical stimulation of the ventromedial nucleus and the dorsomedial nucleus on the activity of tuberoinfundibular dopaminergic neurons.

Perikarya and terminals of tuberoinfundibular dopaminergic (TIDA) neurons are located in the arcuate nucleus (ARN) and in the median eminence (ME), respectively. Dopamine (DA) released from TIDA terminals in the ME inhibits prolactin secretion from the anterior pituitary. Anatomical studies have described the sources of afferents to ARN and ME, but not to TIDA neurons per se. The ventromedial nucleus (VMN) and the dorsomedial nucleus (DMN) of the hypothalamus project to ARN and ME and have a role in prolactin regulation. In the present study, VMN and DMN were investigated as possible sources of TIDA afferents. Alterations in the activity of TIDA neurons were estimated by measuring plasma concentrations of prolactin and the rates of DA synthesis (3,4-dihydroxyphenylalanine - DOPA - accumulation after administration of the decarboxylase inhibitor NSD 1015) and metabolism (concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid - DOPAC) in the ME following electrical stimulation of ARN, VMN, and DMN in ovariectomized female rats. Thirty minutes of bilateral stimulation of ARN or DMN increased DOPA accumulation in the ME; stimulation of the VMN had no effect. 5-Hydroxytryptamine synthesis in the ME was unaffected by stimulation of any region. Plasma prolactin levels declined during DMN stimulation, varying with the frequency and duration of the electrical stimulus. DA metabolism within TIDA neurons increased with DMN stimulation, as evidenced by increased DOPAC concentrations in the ME. In females whose basal TIDA activity has been increased by haloperidol treatment or decreased by bromocriptine treatment, DMN stimulation was still able to increase DOPA accumulation in the ME. The present data suggest the presence of stimulatory TIDA afferents originating from or passing through the DMN.

Lack of evidence for an impairment of tuberoinfundibolar dopaminergic neurons in aged male rats of the Sprague-Dawley strain.

Circulating prolactin (PRL) levels, dopamine (DA) content, in vitro basal and stimulus-evoked endogenous DA release from arcuate-periventricular nuclei median-eminence fragments were studied in young (4 months) and old (24-25 months) male rats of Sprague-Dawley strain. Serum PRL levels did not differ in young and aged animals. In addition DA tissue content, basal and K+- or d-amphetamine evoked endogenous DA release did not show age-related differences. These results suggest that in male rats of the Sprague-Dawley strain the activity of tuberoinfundibular dopaminergic (TIDA) neurons does not change during senescence, unlike what happens in other strains of rats.

Restraint stress decreases the neurosecretory activity of tuberoinfundibular dopaminergic neurons in young but not in aged female rats.

The regulation of prolactin secretion by tuberoinfundibular dopamine (DA) neurons appears to be altered in the aged rat: the concentration of prolactin in the serum increases and the activity of the tuberoinfundibular DA neurons decreases. In the young female rat a brief period of stress reduces the tuberoinfundibular DA neurosecretory activity and increases the secretion of prolactin. The purpose of the present study was to determine if the responsiveness of tuberoinfundibular DA neurons to restraint stress is altered in the aged female rat. The activity of these neurons was estimated from the rate of DA synthesis in their terminals in the median eminence, as measured by the rate of accumulation of dihydroxyphenylalanine (DOPA) after the administration of a decarboxylase inhibitor. Thirty minutes of restraint stress increased serum prolactin concentrations in both young (3 months) and aged (26 months) constant estrous rats, but reduced the rate of DOPA accumulation in the median eminence of only the young rats. Restraint also decreased the rate of DOPA accumulation in the median eminence of intermediate-aged rats (14 months) independently of whether the rats were exhibiting normal ovarian cycles (measured on the day of estrus) or were in a constant estrus. This suggests that the loss of ovarian cyclicity per se is not associated with the age-related change in the response of tuberoinfundibular DA neurons to restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hyperprolactinemia on plasma prolactin and glucose and on local cerebral glucose utilization.

Elevated blood levels of prolactin increase the synthesis, turnover, and release of 3,4-dihydroxyphenylethylamine (dopamine) from the tuberoinfundibular dopaminergic neurons, which project to the median eminence. The present study examined whether hyperprolactinemia also increases local cerebral glucose utilization, as determined by the 2-deoxy-D-[1-14C]glucose method, in the median eminence and other brain structures. Adult male rats were given ovine prolactin (4 mg/kg) subcutaneously every 8 h for 48 h. This treatment exerted an autoregulatory feedback effect on endogenous rat prolactin secretion, as evidenced by decreased circulating levels of rat prolactin. Ovine prolactin treatment also decreased plasma glucose concentrations. However, in both partially immobilized and free-ranging rats, glucose utilization in brain structures containing tuberoinfundibular dopaminergic cell bodies (the arcuate nucleus) and terminals (the median eminence) was not affected by ovine prolactin treatment. Hyperprolactinemia was, however, associated with decreased glucose utilization in the medial forebrain bundle and the CA subfield of the dorsal hippocampus. The lack of a significant effect of prolactin treatment on glucose utilization in the median eminence indicates that the resolution of the deoxyglucose technique, as used here, is not adequate to detect the ovine prolactin-induced increase in tuberoinfundibular dopaminergic neuronal activity, that the median eminence does not utilize glucose as its primary energy substrate, or that ovine prolactin treatment causes a counterbalancing decrease in the activity of other neurons projecting to the median eminence.

Effects of gonadal steroids on tuberoinfundibular and tuberohypophysial dopaminergic neuronal activity in male and female rats.

The activities of tuberoinfundibular and tuberohypophysial dopamine (DA) neurons were estimated by measuring the turnover of DA in terminals of these neurons in the median eminence and in the neural and intermediate lobes of the pituitary, respectively. The rate of DA turnover (alpha-methyltyrosine-induced decline of DA) in the median eminence was two to three times faster in females than in males, but no sexual differences in DA turnover rates were noted in the neural and intermediate lobes. Two weeks following gonadectomy the rate of DA turnover in the median eminence was increased in the male but decreased in the female. These effects were reversed by testosterone and estrogen replacement in gonadectomized males and females, respectively. Neither gonadectomy nor steroid replacement altered DA turnover in the neural or intermediate lobes of either males or females. These results indicate that estrogen stimulates and testosterone inhibits tuberoinfundibular DA neuronal activity while neither steroid affects tuberohypophysial DA neuronal activity.

Prolactin release and tuberoinfundibular dopaminergic neuronal activity following single and double injections of morphine

It is well established that opiate agonists alter tuberoinfundibular dopaminergic activity and consequently prolactin release. The purpose of this study was to characterize the effects of morphine on prolactin secretion and tuberoinfundibular dopaminergic neuronal activity with respect to time after administration. Additionally, the effect of an initial morphine injection on the response produced by a second injection of morphine was determined. The rate of depletion of median eminence dopamine content following synthesis inhibition byα-methyl- p-tyrosine was used as an index of dopaminergic neuronal activity. Male rats given a single injection of morphine sulfate (15 mg/kg, s.c.) showed a significant increase in circulating prolactin levels and had a lower rate of median eminence dopamine turnover 1 h after injection. Four hours after injection, circulating prolactin levels were similar to those in vehicle treated rats, while dopamine turnover was significantly higher than controls. When two injections of morphine sulfate (15 mg/kg, s.c.) were given 4 h apart, the stimulation of prolactin release produced by the second injection was significantly attenuated. Although this second injection caused a significant decrease in dopamine turnover, the turnover rate following this injection was significantly greater than that following the initial injection. The combination of fluoxetine and 5-hydroxytryptophan (FLX/5-HTP) caused an initial increase in prolactin secretion with plasma values returning to basal levels by 4 h. When rats were pretreated with FLX/5-HTP instead of morphine, the prolactin response to an injection of morphine 4 h later was not attenuated. Similarly a FLX/5-HTP pretreatment had no influence on a second injection of FLX/5-HTP administered 4 h later. The attenuation of a secretory response to a second morphine injection is specific to prolactin, since the growth hormone responses to the initial and the second injections of morphine were the same. These results indicate that the response of tuberoinfundibular dopaminergic neurons to morphine is biphasic. Following morphine administration, dopamine turnover is initially decreased but by 4 h turnover is increased above pretreatment rates. These alterations in dopamine turnover affect prolactin secretion such that release is initially stimulated, but 4 h later the response to a second morphine stimulation is attenuated.

Histamine-induced prolactin release and activity of tuberoinfundibular dopaminergic neurons in male rats.

The role of tuberoinfundibular dopamine (DA) in the histamine-induced rise of plasma prolactin was studied in male rats. Right lateral ventricle (icv) histamine injection (30 micrograms/rat) caused a significant rise of plasma prolactin at 15 and 30 min; at 60 min values returned to basal levels. Histamine does not modified steady-state DA concentrations. For turnover evaluation, histamine was icv injected immediately or 30 min after the tyrosine hydroxylase inhibitor alpha-methyltyrosine (250 mg/kg i.p.) and DA concentration in the median eminence was measured at 0, 1 and 2 hours after the inhibitor injection. Rate constants of DA decline and DA synthesis rates were found similar in both controls (cerebrospinal fluid) and histamine-injected rats. These results indicate that the stimulatory action of histamine on prolactin release might not be associated to DA. It would be due mainly to its action on prolactin-releasing factors and to a minor extent, to changes in the dopaminergic system.

The rapid 'tonic' and the delayed 'induction' components of the prolactin-induced activation of tuberoinfundibular dopaminergic neurons following the systemic administration of prolactin.

The present study was designed to characterize the time and dose relationships of the response of tuberoinfundibular dopaminergic (TIDA) neurons in the rat to systemically administered prolactin (PRL). The activity of TIDA neurons was estimated by measuring the rate of dopamine (DA) synthesis in the median eminence (DOPA accumulation following the administration of a decarboxylase inhibitor). Rats were pretreated with bromocriptine, a dopaminergic agonist, so as to inhibit the release of endogenous PRL from the anterior pituitary, and thereby reduce the activity of TIDA neurons to a 'basal' level from which it could be increased subsequently by exogenously administered PRL. In control animals an intraperitoneal injection of ovine PRL (oPRL) increased DOPA accumulation at 16 h, but not before, whereas in bromocriptine-pretreated animals an intraperitoneal injection of oPRL increased DOPA accumulation after 4 h ('tonic' component) and caused a further increase after 16 h ('induction' component). Continuous intravenous infusions of oPRL into bromocriptine-pretreated rats increased DOPA accumulation in the median eminence by 4 h, and when infused into control rats oPRL reduced serum concentrations of endogenous rat PRL (rPRL) by 2 and 4 h. Continuous intravenous infusions of rPRL increased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an 'all-or-none' response). TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h. Three daily injections of haloperidol elevated circulating rPRL concentrations and increased the rate of DOPA accumulation in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of low hypothalamic dopaminergic activity after removal of chronic estrogen treatment.

The purpose of this study was to determine whether inhibition of tuberoinfundibular dopaminergic (TIDA) neuron function which occurs during chronic estrogen administration persists after removal of the estrogen. Ovariectomized (OVX) Fischer 344 (F344) rats were implanted for 4 weeks with a Silastic capsule containing estradiol-17 beta (E2) and controls with an empty capsule for 4 weeks. Other rats which received E2 for 4 weeks had the capsule removed and experiments performed 4 weeks later. At the end of 4 weeks of E2 treatment, anterior pituitary (AP) weight was increased sixfold, serum prolactin (PRL) 65-fold, and AP DNA content fivefold over OVX control rats. Four weeks after removal of E2, AP weight, serum PRL, and AP DNA content declined, but remained significantly above OVX control values. At the end of 4 weeks of E2 treatment and after E2 withdrawal, release of [3H]dopamine (DA) from median eminence (ME) tissue superfused in vitro was lower than from ME of OVX control rats although [3H]DA accumulation was not significantly different among the treatment groups. Administration of apomorphine (APO), a dopamine agonist, significantly reduced plasma prolactin levels in OVX control rats, in rats at the end of 4 weeks E2 treatment, and in rats after 4 weeks of E2 withdrawal. Injection of haloperidol (HALO) produced similar increases in plasma PRL/estimated PRL-cell DNA in OVX controls, at the end of E2 treatment or after E2 withdrawal. However, injection of morphine (MOR), a drug which increases the release of PRL by inhibiting hypothalamic dopaminergic activity, resulted in a rise in plasma PRL/estimated PRL-cell DNA in OVX control rats that was significantly greater compared to rats at the end of E2 treatment or after E2 withdrawal. Since rats treated with E2 released less [3H]DA from ME tissue in vitro, and were less responsive to MOR, it can be that animals treated for 4 weeks with E2 show a decreased ability to release DA from TIDA neurons which persists even after termination of E2 treatment. These results suggest that chronic high circulating E2 levels result in a depression of TIDA neuronal activity which is sustained after E2 is removed.

Differential effects of morphine on the rates of dopamine turnover in the neural and intermediate lobes of the rat pituitary gland

The acute adminstration of morphine to male rats decreased the rate of dopamine turnover in the median eminence and in the neural lobe of the pituitary, but was without effect in the intermediate lobe of the pituitary. Pretreatment with the opiate antagonist, naltrexone, reduced the effects of morphine. These results indicate that morphine, by acting on opiate receptors, inhibits the activity of tuberoinfundibular dopaminergic neurons that terminate in the median eminence and those tuberohyphysial dopaminergic neurons that terminate in the neural lobe of the pituitary.

Acute Restraint Stress Decreases Tuberoinfundibular Dopaminergic Neuronal Activity: Evidence for a Differential Response in Male versus Female Rats

The basal activity o f tuberoinfundibular dopaminergic (TIDA) neurons is higher and the response of these neurons to the stimulatory actions of prolactin is greater in the female than in the male rat. In the female rat, the restraint-stress-induced increase in serum prolactin concentrations is accompanied by a concurrent decrease in the activity of TIDA neurons. The purpose of the present study was to compare these effects of restraint in male and female rats. TIDA neuronal activity was estimated by measuring the rate of dopamine (DA) synthesis (DOPA accumulation after the administration of a decarboxylase inhibitor, NSD 1015) and the rate of DA turnover (decline of DA after administration of a tyrosine hydroxylase inhibitor; alpha-methyltyrosine) in the median eminence. Thirty minutes of restraint increased serum prolactin concentrations in both male and female rats, but a greater response was observed in the females. Restraint also decreased the rates of synthesis and turnover of DA in the median eminence of the female but not the male rat. The difference in the response of TIDA neurons in male and female rats to restraint is not the consequence of neuronal differentiation resulting from neonatal androgen exposure, because restraint aso decreased the activity of TIDA neurons in androgen-sterilized female rats. The inability of restraint stress to reduce TIDA neuronal activity in the male rat appears to be the consequence of testosterone, since TIDA neurons were responsive to restraint following castration of the males.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute restraint stress decreases dopamine synthesis and turnover in the median eminence: a model for the study of the inhibitory neuronal influences on tuberoinfundibular dopaminergic neurons.

The effects of acute stress on serum prolactin concentrations and tuberoinfundibular dopaminergic (TIDA) neuronal activity were studied in female rats. TIDA neuronal activity was estimated by measuring the rate of dihydroxyphenylalanine (DOPA) accumulation after the administration of a decarboxylase inhibitor (NSD 1015) and the rate of decline of dopamine (DA) after the administration of a tyrosine hydroxylase inhibitor (alpha-methyltyrosine) in the median eminence. Serum prolactin concentrations were increased following 30 min of supine immobilization (restraint stress), but returned to control levels by 2, 8, and 16 h after the onset of this stress. The rate of DOPA accumulation was decreased during the 30 min of restraint; it was still further reduced 2 h later but had returned to control levels 8 and 16 h later. No change in the rate of DOPA accumulation was observed in the striatum or neurointermediate lobe of the pituitary at any time after the start of restraint. Restraint stress also decreased the rate of DA turnover in the median eminence, but was without effect on the rates of DA turnover in the striatum or neurointermediate lobe. These results suggest that restraint stress activates an inhibitory neuronal pathway which decreases the activity of TIDA neurons and may be responsible, at least in part, for the increase in serum prolactin concentrations. The responsiveness of TIDA neurons to the stress-induced decrease in activity was not influenced by the time of day or the stage of the estrous cycle. Not all stressful manipulations decreased TIDA neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoprolactinemia induced by hypophysectomy and long-term bromocriptine treatment decreases tuberoinfundibular dopaminergic neuronal activity and the responsiveness of these neurons to prolactin.

The effect of long-term decreases in circulating concentrations of prolactin was determined on the responsiveness of tuberoinfundibular dopamine (DA) neurons to this hormone. The activity of these neurons in ovariectomized rats was estimated by measuring the rate of DA synthesis (DOPA accumulation after the administration of a decarboxylase inhibitor) in the median eminence at various times after serum concentrations of prolactin had been reduced by hypophysectomy or the chronic administration of a DA agonist (bromocriptine, 3 mg/kg/day). The concentration of DA in the median eminence, but not in striatum, declined progressively up to 12 days after hypophysectomy, but did not change at any time during bromocriptine treatment. On the other hand, norepinephrine concentrations in the median eminence were increased 12 days after both treatments. Within 24 h after hypophysectomy or the first injection of bromocriptine the rate of DA synthesis in the median eminence was decreased; this decrease was maintained for at least 12 days suggesting that tuberoinfundibular DA neuronal activity is normally maintained by endogenous prolactin. Intracerebroventricular (ICV) injections of prolactin (10 micrograms, 12 h prior to sacrifice) increased the rate of DA synthesis in the median eminence of control, 24-hour hypophysectomized and 24-hour bromocriptine-treated rats. After longer periods (6-12 days) of bromocriptine treatment or after hypophysectomy the responsiveness of tuberoinfundibular DA neurons to prolactin was reduced. Dose-response studies revealed that the sensitivity and magnitude of response to ICV prolactin was markedly reduced in 12-day hypophysectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid 'tonic' and a delayed 'induction' component.

Results of previous studies have revealed that prolactin causes a delayed (12-16 h) increase in the rate of synthesis and turnover of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence. Attempts to demonstrate a rapid in vivo action of prolactin on these neurons has been frustrated because pharmacological manipulations needed to make the biochemical measurements of TIDA neuronal activity (i.e., administration of alpha-methyltyrosine or NSD 1015) inhibit DA synthesis and thereby remove the tonic inhibitory control of DA on prolactin secretion. Thus, 'control' rates of synthesis and turnover of DA in terminals of TIDA neurons are actually values obtained in the presence of high circulating concentrations of prolactin. Results of the present in vivo studies demonstrate that there are two components to the activation of TIDA neurons by prolactin: a rapid 'tonic' component, which is responsive to acute changes in prolactin concentrations, and a delayed 'induction' component, which is activated by long-term changes in prolactin concentrations. Experimental observations which support this proposal are described below. Hypophysectomy or treatment with bromocriptine (a DA agonist) reduce circulating levels of prolactin and reduce the rate of DA synthesis in the median eminence. Intracerebroventricular (i.c.v.) administration of prolactin to these animals increases the rate of DA synthesis in the median eminence within 4 h (rapid 'tonic' component) and then causes a further increase after 12 h (delayed 'induction' component); only the latter component is blocked by treatment with cycloheximide, indicating the involvement in protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Placental lactogen mimics prolactin in activating tuberoinfundibular dopaminergic neurons

The phasic patterns of prolactin release and tuberoinfundibular dopaminergic (TIDA) neuronal activity which occur during early pregnancy in the rat cease by midpregnancy. It has been suggested that this cessation is mediated by the increased secretion of placental lactogen which occurs at this time. The present experiments were undertaken to assess the effects of placental lactogen on TIDA neurons. The activity of these neurons was estimated from the in vivo rate of dihydroxyphenylalanine (DOPA) accumulation in the median eminence after the administration of an inhibitor of aromatic l-amino acid decar☐ylase. Female rats, ovariectomized 2 weeks previously, were injected intraventricularly (i.c.v.) 12 h prior to sacrifice with either rat prolactin (10 μg), human placental lactogen (100 μg) or 0.9% saline vehicle. The human placental lactogen increased the rate of DOPA accumulation in the median eminence, as did rat prolactin, suggesting that placental lactogen is capable of mimicking prolactin in activating TIDA neurons. Human placental lactogen (10–100 μg/10 μl, i.c.v.) stimulated TIDA neurons in a time-related manner reminiscent of that obtained with prolactin (i.e. the neurons were activated at 12 and 16 h but not at 4 or 8 h after i.c.v. infusion of prolactin). These actions of placental lactogen are not due to its somatotrophic properties, since low doses of rat growth hormone were without effect on these neurons. These data indicate that placental lactogen, acting in a prolactin-like fashion, can stimulate TIDA neurons.

Role of prolactin feedback in the semicircadian rhythm of tuberoinfundibular dopaminergic neuronal activity during early pregnancy in the rat.

During the first half of pregnancy rats exhibit a diurnal-nocturnal pattern of tuberoinfundibular dopaminergic (TIDA) neuronal activity, which is directly out of phase with the diurnal-nocturnal surges of prolactin secretion. To determine if the pattern of TIDA neuronal activity is maintained by a prolactin feedback mechanism the serum concentrations of this hormone were manipulated in the 6-day pregnant female by pharmacological means. TIDA neuronal activity was estimated in vivo by measuring the rate of dopamine synthesis (the rate of dihydroxyphenylalanine (DOPA) accumulation after the administration of an inhibitor of aromatic L-amino acid decarboxylase) in the median eminence, the region that contains the terminals of these neurons. In vehicle-treated pregnant rats cyclical changes in serum prolactin concentrations were observed, with peaks occurring at 06.00 and 21.00 h and a nadir (basal level) at 12.00 h. At the same time there was a diurnal-nocturnal pattern in the rate of DOPA accumulation in the median eminence with low values occurring at 03.00–06.00 and 18.00–21.00 h and a higher ‘basal’ value at 12.00 h. Pretreatment with bromocriptine, a long-acting dopaminergic agonist 24 h prior to sacrifice, maintained serum prolactin concentrations at very low values (<25 ng/ml) throughout day 6 of pregnancy. As a result of the low circulating concentrations of prolactin the rate of DOPA accumulation in the median eminence was reduced so that the diurnal-nocturnal pattern of TIDA neuronal activity was lost. On the other hand, pretreatment with haloperidol, a dopaminergic antagonist, 24 h prior to sacrifice increased serum concentrations of prolactin throughout the day (>700 ng/ml) such that the diurnal-nocturnal pattern was eliminated. As a result of the haloperidol-induced increase of serum prolactin concentrations the rate of DOPA accumulation in the median eminence was increased, but the diurnal-nocturnal pattern was maintained. Similarly, an intracerebroventncular injection of prolactin 12 h prior to sacrifice increased the rate of DOPA accumulation in the median eminence, but did not disrupt the characteristic pattern of activity in the TIDA neurons. The results of the latter two experiments suggest that the cyclical pattern of TIDA neuronal activity which occurs in day 6 pregnant rats is not the result of the diurnal-nocturnal surges of prolactin which occur in these-animals. On the other hand, the ‘basal’ activity of TIDA neurons in the early pregnant rat is ‘set’ by the serum concentration of prolactin just as it is in male and nonpregnant female rats.

Role of a uterine-placental factor in the cessation of the semicircadian rhythm of tuberoinfundibular dopaminergic neuronal activity at midpregnancy in the rat.

During early pregnancy in the rat, the secretion of prolactin exhibits daily surges which appear to be related temporally to changes in the activity of tuberoinfundibular dopaminergic (TIDA) neurons.