Richard H. Alper

Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems

On the basis of biochemical indices of dopamine (DA) nerve activity (decline of DA after inhibition of tyrosine hydroxylase, accumulation of DOPA after inhibition of DOPA decarboxylase) it was revealed that morphine increases the activity of nigrostriatal and mesolimbic DA nerves which terminate in the striatum, nucleus accumbens and olfactory tubercle, but reduce the activity of tuberoinfundibular DA nerves which terminate in the median eminence. Morphine had no effect on tuberohypophyseal DA nerves which project to the posterior pituitary. Naloxone was without effectper se, but blocked the effects of morphine on DOPA accumulation. Thus, morphine differentially alters the diverse DA neuronal systems in the rat brain.

Dehydration Selectively Increases Dopamine Synthesis in Tuberohypophyseal Dopaminergic Neurons

The concentration of dopamine (DA) and the accumulation of DOPA following the administration of a decarboxylase inhibitor were determined in the rat striatum, median eminence and posterior pituitary, regions containing terminals of nigrostriatal, tuberoinfundibular and tuberohypophyseal DA nerves, respectively. Severe dehydration (2 days water deprivation followed by 3 days of 2% NaCl substituted for drinking water) increased the concentration of DA in the posterior pituitary but not in the striatum or median eminence. Less severe dehydration caused by 2 or 3 days of water deprivation did not alter steady state concentrations of DA, but increased DOPA accumulation, an index of DA nerve activity, only in the posterior pituitary. Food deprivation for 3 days did not alter DOPA accumulation in the posterior pituitary. These results suggest that dehydration selectively activates the tuberohypophyseal DA neuronal system in the rat.

Dopa accumulation is a measure of dopamine synthesis in the median eminence and posterior pituitary.

A radioenzymatic assay was employed to measure the accumulation of DOPA in a variety of rat brain tissues 30 min after the administration of a decarboxylase inhibitor in order to estimate the activity of dopamine (DA) nerves which terminate in these regions. In the median eminence and posterior pituitary the accumulation of DOPA appears to occur primarily in DA nerves since: (1) the rate of synthesis of norepinephrine (NE), as estimated from theα-methyltyrosine-induced decline of catecholamines, accounts for less than 10% of total catecholamine synthesis in these two brain regions; and (2) the accumulation of DOPA is not significantly altered when the NE concentrations in these regions are reduced to 40–50% of control by prior intraventricular injections of 6-hydroxydopamine. These results suggest that the accumulation of DOPA in the median eminence and the posterior pituitary can be used to estimate the activity of tuberoinfundibular and tuberohypophyseal DA nerves, respectively.

Effects of surgical sympathectomy on catecholamine concentrations in the posterior pituitary of the rat

Approximately one-third of the norepinephrine in the posterior pituitary of the rat is contained in terminals of sympathetic nerves which originate in the superior cervical ganglia; the remaining norepinephrine and dopamine appear to be in nerves of central origin.

Effect of paraquat treatment of rats on disposition of 5-hydroxytryptamine and angiotensin I by perfused lung.

Abstract Rats were injected with the herbicide, paraquat dichloride (25 mg/kg, i.p.), and their lungs were perfused 2–28 days later. Isolated lungs from rats treated with paraquat (PQ) 3 or 4 days before perfusion removed significantly less perfused 5-hydroxytryptamine (5-HT) than did saline-injected controls. This effect was not caused by PQ directly, since perfusion of lungs from untreated animals with PQ did not alter removal of co-perfused 5-HT. Monoamine oxidase activity of600 g supernatan fractions of homogenates of lungs from PQ-treated rats was also reduced compared to controls. Although removal of perfused angiotensin I (1 ng/ml) by isolated lungs was not altered by PQpretreatment, antgiotensin-converting enzyme activity in 600 g supernatant fractions of lung homogenates was reducedd significantly. These results suggest that PQ damages pulmonary endothelium and impairs the metabolic function of lung.

Changes in the Rate of Dopamine Synthesis in the Posterior Pituitary during Dehydration and Rehydration:Relationship to Plasma Sodium Concentrations

The rate of DOPA accumulation after the administration of a decarboxylase inhibitor (an in vivo estimate of dopamine synthesis) was determined in rat posterior pituitary, median eminence and striatum, regions containing terminals of tuberohypophyseal, tuberoinfundibular and nigrostriatal dopamine neurons, respectively. 3 days of water deprivation increased the hematocrit and the plasma sodium concentration and also increased the rate of DOPA accumulation in the posterior pituitary, but not in the striatum or median eminence. Water deprivation or substitution of 2% NaCl for drinking water for 5 days increased DOPA accumulation in the posterior pituitary and the plasma sodium concentration, while the hematocrit was increased only in the water-deprived group. Following 3 days of water deprivation, access to water for 3 h caused the elevated DOPA accumulation in the posterior pituitary and the plasma sodium concentration to return to control values while the hematocrit remained slightly elevated. Substitution of 2% NaCl for drinking water for 48 h to rats which had been water-deprived for 3 days restored the hematocrit to control, but did not alter the water deprivation induced increase in plasma sodium concentration or the rate of DOPA accumulation in the posterior pituitary. These results suggest that tuberohypophyseal dopaminergic neurons are regulated, at least in part, by sodium or osmoreceptors.

Injection of Hypertonic Saline or Mannitol Accelerates the Dehydration-Induced Activation of Dopamine Synthesis in the Neurointermediate Lobe of the Rat Hypophysis

The rate of dopamine (DA) synthesis (DOPA accumulation after the administration of an inhibitor of aromatic L-amino acid decarboxylase) was determined in terminals of tuberohypophyseal DA neurons in the neurointermediate lobe (NIL) of the rat hypophysis at various times after the presentation of osmotic stimuli. DA synthesis in the NIL, but not in median eminence or striatum, was increased 24 h but not 4 h after an injection of hypertonic saline (5 ml 15% NaCl/kg, s.c.), provided the animals were not permitted access to water after the injection; 24 h of water deprivation per se was without effect on the rate of DA synthesis. DOPA accumulation in the NIL was also increased after an intravenous infusion of mannitol (25 ml 20% mannitol/kg) plus 24 h of water deprivation. These results suggest that the dehydration-induced activation of tuberohypophyseal DA neurons which is normally seen after 2-3 days of water deprivation can be accelerated if water deprivation is preceeded by injections of hypertonic saline or mannitol.