Administration Of Alpha-methyltyrosine Research Articles

Effect of dopamine agonists and antagonists on the binding of [3H]estradiol to its receptors in the anterior pituitary gland of male rats.

The synthesis of PRL and DNA in PRL cells is regulated by estrogens and dopamine. To investigate a possible relationship between these two components, we studied the influence of dopamine agonists and antagonists on the binding of [3H]estradiol ([3H]E2) to its receptors in the anterior pituitary gland of estrogenized male rats. The administration of sulpiride (dopamine antagonist) or bromocriptine (dopamine agonist) decreased the binding of [3H]E2 to cytosolic receptors when the concentration of [3H]E2 in the assay mixture was 1 nM. Both drugs also diminished the binding of [3H]E2 when they were added in vitro to the incubation media, apparently in a competitive way. Dopamine and alpha-methyltyrosine also inhibited competitively the binding of [3H]E2 to cytosolic receptors. The inhibition constants were determined by the Lineweaver-Burk plot. To overcome the competitive inhibition of dopamine agonists and antagonists, the concentration of the titrated steroid in the incubation mixture was increased to 16 nM. This concentration was established by saturation analysis. The administration of alpha-methyltyrosine increased the binding of [3H]E2 to nuclear receptors without modifying the binding to cytosolic receptors. This increase paralleled an increment in the levels of plasma PRL. Bromocriptine prevented the increase in [3H]E2 binding produced by alpha-methyltyrosine and had no effect on the binding when administered to nontreated rats. These results suggest that dopamine can regulate the biological effects of estradiol in the anterior pituitary gland by decreasing the binding of this hormone to its receptors.

Influence of renal nerves on noradrenergic responses to changes in arterial pressure.

Renal denervation has been shown previously to lower the increased arterial pressure as well as the increased hypothalamic and peripheral noradrenergic activity found in neurogenic and Goldblatt models of experimental hypertension. In the present study conscious Wistar rats with or without renal nerves were subjected to 60 min of saline infusion (controls), hypotension (intravenous sodium nitroprusside), or hypertension (intravenous phenylephrine HCl). Changes in the turnover of norepinephrine (NE) in the anterior hypothalamus, posterior hypothalamus, kidney, intestine, and skeletal muscle were assessed by measuring the decline of NE concentration 90 min after administration of alpha-methyl tyrosine. There was a significant increase in NE turnover in the posterior hypothalamus and all peripheral organs examined in the nitroprusside-infused group with intact renal nerves. In renal-denervated animals, acute hypotension produced similar changes in NE turnover in peripheral organs, but no significant change was observed in the posterior hypothalamus. In the acutely hypertensive group with intact renal nerves, there was no significant change in NE turnover in the hypothalamic sections or the peripheral organs; however, the turnover of NE was significantly decreased in both the anterior and posterior hypothalamus of the renal-denervated hypertensive group. Overall these studies suggest the presence of an interaction between inhibitory influences from baroreceptor afferents and excitatory influences from renal afferents on noradrenergic activity in the hypothalamus and changes in noradrenergic activity in hypothalamic structures may not be directly related to changes in sympathetic outflow.

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)

Behavioral and biochemical studies of the scopolamine-induced reversal of neuroleptic activity.

Scopolamine reversed the reduction in avoidance responding caused by spiperone and antagonized the inhibitory effects of spiperone on the behavioral actions of d-amphetamine or apomorphine. Scopolamine-induced locomotor activity was greater in 6-hydroxydopamine (6-OHDA)-treated animals than in controls. This increase was prevented by administration of alpha-methyltyrosine, but not by inhibition of dopamine-beta-hydroxylase, indicating that this action of scopolamine was associated with presynaptic dopaminergic fibers. Therefore, the possibility that pre-synaptic dopaminergic function was the locus of the antagonism of spiperone by scopolamine was examined using drug interaction studies in 6-OHDA-treated rats. However, when 6-OHDA-treated rats were given alpha-methyltyrosine, scopolamine still reversed the spiperone blockade of apomorphine-induced locomotion. Although these data provided evidence for a post-synaptic action for this cholinergic blocking agent, scopolamine affected neither dopamine-stimulated adenylate cyclase activity nor 3H-spiperone binding in vitro. Furthermore, scopolamine did not alter the level of specific 3H-spiperone binding found in brain after in vivo administration. This suggests that the post-synaptic mechanism affected by scopolamine is different from the site affected by spiperone. Thus, it is concluded that scopolamine can affect both pre- or post-synaptic events associated with dopaminergic function and that both may contribute to the reversal of the actions of spiperone.

Methylphenidate and d-amphetamine: effects and interactions with alphamethyltyrosine and tetrabenazine on DRL performance in rats.

The effects of d-amphetamine and methylphenidate and their interactions with amine-depleting drugs were examined in rats trained to press a lever to obtain water reinforcement on a schedule that differentially reinforced responding at low rates (DRL). Both methylphenidate (2.5-20.0 mg/kg) and d-amphetamine (0.375-3.0 mg/kg) increased the rate of responding and decreased the frequency of reinforcement on the DRL schedule. Both drugs also shifted the interresponse time (IRT) distributions to the left such that the modal IRT occurred well below the minimum IRT required for reinforcement (d-amphetamine was abut eight times more potent than methylphenidate for each of these effects). The effects of both d-amphetamine and methylphenidate on DRL performance were attenuated by administration of alphamethyltyrosine (AMT) (150 mg/kg) and both drugs attenuated the response rate-suppressing effects of tetrabenazine (TBZ) (4.0 mg/kg). The similarity of the drug interactions between methylphenidate or amphetamine and AMT or TBZ suggest that the doses of methylphenidate and d-amphetamine examined act on similar catecholaminergic pools with the central nervous system to influence DRL performance.

Acute homeostatic imbalances reinstate sensorimotor dysfunctions in rats with lateral hypothalamic lesions.

It has previously been demonstrated that rats recovered from aphagia and adipsia after large bilateral electrolytic lesions of the lateral hypothalamic area do not show the normal feeding response to 2-deoxyglucose or drinking response to polyethylene glyol. The present work reveals that such homeostatic imbalances reinstate the profound sensorimotor impairments that are seen in the immediate postoperative period but abate in parallel with the gradual recovery of ingestive behaviors. Administration of alpha-methyltyrosine or spiroperidol produced sensory and motor dysfunctions in rats with lateral hypothalamic lesions that were similar to those observed after 2-deoxyglucose. These results suggest that the residual feeding and drinking deficits of rats with lateral hypothalamic lesions after apparent recovery of function do not reflect specific loss of putative gluco- and volume-regulatory contributions to ingestive behavior. Instead, they may indicate continued impairments in nonspecific activational components of motivation that normally are mediated, in part, by central dopaminergic neurons.

Role of Catecholamines in Photoperiodically-Induced Gonadal Development in Coturnix Quail1

The involvement of central biogenic amines in the mechanisms controlling photoperiodically-induced testicular development in Coturnix quail were studied employing pharmacological approaches. Daily administration of alpha-methyltyrosine (MT), which blocks catecholamine (CA) biosynthesis, to 6-week-old quail exposed to long daily photoperiods markedly depleted brain dopamine (DA), norepinephrine (NE) and epinephrine (E). This was associated with a partial suppression of testicular growth 7 days after light stimulation. Combined treatment with MT and L-dihydroxyphenylalanine (L-DOPA), a precursor of DA, NE and E, elevated the monoamine levels in the brain and prevented the blocking effect of MT on testicular growth. Selective blockade of NE and E biosynthesis with diethyl-dithiocarbamate (DDC) depleted both NE and E, while it elevated DA level. Furthermore, such treatment reduced testicular weight. In DDC-treated birds, D,L-dihydroxyphenylserine (DL-DOPS) administration, which bypasses the DDC block, restored only brain NE level and reversed the blocking action of DDC on testicular weight. It is concluded that central NE plays a role in transformation of the photoperiodic information affecting gonadal development in Coturnix quail.

Recovery of feeding and drinking by rats after intraventricular 6-hydroxydopamine or lateral hypothalamic lesions.

Rats given intraventricular injections of 6-hydroxydopamine after pretreatment with pargyline become aphagic and adipsic, and show severe loss of brain catecholamines. Like rats with lateral hypothalamic lesions, these animals gradually recover ingestive behaviors, although catecholamine depletions are permanent. Both groups decrease food and water intakes markedly after the administration of alpha-methyltyrosine, at doses that do not affect the ingestive behaviors of control rats. Thus, both the loss and recovery of feeding and drinking behaviors may involve central catecholamine-containing neurons.

Adrenergic innervation of the cerebral blood vessels in the rabbit.

✓ The Hillarp technique of fluorescent staining of monoamines was used to examine the adrenergic fibers in the cerebral vessels of rabbit brains. These fibers were found to lie wholly within the deeper layers of the adventitia and not within muscle layers. Varicosities were interpreted as representing neural transmitter substance. The basilar artery had a sparse innervation; the anterior cerebral, carotid, and middle cerebral arteries were more richly supplied by adrenergic terminals, with the most dense innervation in the superficial vessels between 100 and 300 µ in diameter. Mild trauma to the basilar artery, as well as subarachnoid blood without trauma, caused the catecholamine reaction to disappear. A marked depletion of adrenergic fibers was also noted after administration of alpha methyl tyrosine and subjection of the animals to extremes of blood pressure.