Absence of D1 dopamine receptors that stimulate prolactin release in the rat pituitary

It has been shown recently that SKF 38393-A (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine-7-ol), a D-1 receptor agonist, possesses a prolactin-releasing effect in the rat, though the pituitary or central nervous system location of the receptors involved has not been clarified. The aim of our study was to elucidate this point. SKF 38393-A administered to freely moving adult female and male rats induced a striking, short-lived increase of basal prolactin levels. The prolactin stimulatory effect of SKF 38393-A was counteracted by pretreatment with SCH 23390, A D-1 receptor blocker. SKF 38393-A (10(-11)-10(-6)M) added to monolayer primary cultures of anterior pituitary cells from rats of both sexes failed to modify prolactin release. At higher concentrations (10(-5)-10(-4) M) the drug induced a slight inhibition of prolactin release. Similarly, SKF 38393-A failed to stimulate adenylate cyclase activity in anterior pituitary membranes from rats of both sexes at low concentrations, while it inhibited enzyme activity at higher concentrations (10(-5)-10(-3) M). The latter effect was counteracted by concomitant addition of the antagonist of D-2 receptors, 1-sulpiride. These data demonstrate that: (1) the anterior pituitary does not contain D-1-dopamine receptors (positively coupled to adenylate cyclase) stimulatory to prolactin release; (2) the striking prolactin-releasing effect of SKF 38393-A in the rat is due to activation of extra-pituitary D-1 dopamine receptors; (3) SKF 38393-A, at high concentrations, is capable of activating pituitary D-2 receptors.     

Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum

Rationale Acute systemic administration of salvinorin A, a naturally occurring κ-opioid receptor (KOPr) agonist, decreases locomotion and striatal dopamine (DA) overflow. Objectives Conventional and quantitative microdialysis techniques were used to determine whether salvinorin A infusion into the dorsal striatum (DSTR) decreases DA overflow by altering DA uptake or release. The influence of repeated salvinorin A administration on basal DA dynamics and cocaine-evoked alterations in DA overflow and locomotion was also assessed. Materials and methods Salvinorin A was administered via the dialysis probe (0; 20–200 nM) or via intraperitoneal (i.p.) injection (1.0 or 3.2 mg/kg per day × 5 days). The effects of a challenge dose of cocaine were examined 48 h after repeated salvinorin treatment. Results Retrodialysis of salvinorin A produced a dose-related, KOPr antagonist reversible, decrease in DA levels. Extracellular DA levels were decreased whereas DA extraction fraction, which provides an estimate of DA uptake, was unaltered. In contrast to its acute administration, repeated salvinorin A administration did not modify dialysate DA levels. Similarly, neither basal extracellular DA levels nor DA uptake was altered. Unlike synthetic KOPr agonists, prior repeated administration of salvinorin A did not attenuate the locomotor activating effects of an acute cocaine (20 mg/kg, i.p.) challenge. However, cocaine-evoked DA overflow was enhanced. Conclusions These data demonstrate that acute, but not repeated, salvinorin A administration decreases mesostriatal neurotransmission and that activation of DSTR KOPr is sufficient for this effect. Differences in the interaction of salvinorin and synthetic KOPr agonists with cocaine suggest that the pharmacology of these agents may differ.     

Effects of the dopamine D2 selective receptor antagonist remoxipride on dopamine turnover in the rat brain after acute and repeated administration

The effects of the dopamine D2 selective receptor antagonist, remoxipride, on dopamine turnover in the rat brain were studied after acute and repeated administration and compared with the effects of haloperidol. Acute administration of remoxipride produced a dose-dependent increase of the concentrations of DOPAC and HVA in both striatum and olfactory tubercle + nucleus accumbens. The maximal effect of both acute remoxipride and haloperidol on dopamine turnover was attained approximately 2 hours after a single intraperitoneal administration, whereas a biphasic response was seen after oral remoxipride. Tolerance to the effects of repeated haloperidol (20 mumol/kg orally) treatment on dopamine turnover was observed as soon as after 3 days, whereas no such tolerance could be found during the first 15 days of repeated treatment with remoxipride (20 mumol/kg orally). A dose-related tolerance to the effects of remoxipride was, however, seen at higher dosages (40, 150 and 600 mumol/kg orally) and after a longer period (6 months) of treatment.     

Oligopeptides interfering with calcium channels inhibit prolactin and growth hormone release by cultured anterior pituitary cells of the rat

A number of oligopeptides, protected at their N termini and possessing an aldehyde residue at their C terminal amino acids, are able to inhibit 45Ca2+ influx into anterior pituitary cells grown in monolayer culture and depolarized with high extracellular potassium concentration. In addition, the same oligopeptides interfere with hormone release, especially with that produced by lactotrophs. Our findings imply that oligopeptides may represent a new class of calcium channel ligands, and the pituitary cells are sensitive targets for them.     

Effects of the benzazepine SCH 23390 on prolactin release from isolated pituitary

The benzazepine, SCH 23390 (10(-5) M), is able to block D2 anterior pituitary receptors and their interaction with a maximal concentration of dopamine (10(-7) M) in an experimental setting involving superfused pituitary slices and prolactin release by lactotrophs as a functional model of such receptors; this finding which correlates nicely with binding studies and drug-induced hyperprolactinaemia supports a SCH 23390 D1 dose-related selectivity; given at doses higher than those inducing behavioural changes, the compound may affect D2 receptor-driven functions, e.g. prolactin secretion.     

Presynaptic nicotinic receptors modulating dopamine release in the rat striatum

The modulation of striatal dopamine release by presynaptic nicotinic acetylcholine receptors is well documented for both synaptosomes and slices. Because the latter retain local anatomical integrity, we have compared [3H]dopamine release evoked by the nicotinic receptor agonists (-)-nicotine and (+/-)-anatoxin-a from striatal synaptosome and slice preparations in parallel. At higher agonist concentrations, mecamylamine-sensitive [3H]dopamine release was greater from slices, indicative of an additional component, and this increase was abolished by glutamate receptor antagonists. To begin to examine the localisation of specific nicotinic acetylcholine receptor subtypes in the striatum, immunogold electron microscopy was undertaken with the beta2-specific monoclonal antibody 270. In striatal sections, gold particles were associated with symmetric synapses (dopaminergic) but were absent from asymmetric synapses (glutamatergic). Surface labelling of striatal synaptosomes with gold particles was also demonstrated. Taken together, these results are consistent with dopamine release mediated by beta2-containing nicotinic acetylcholine receptors on dopamine terminals, while non-beta2-containing nicotinic acetylcholine receptors may enhance dopamine release indirectly by releasing glutamate from neighbouring terminals.     

Characterization of the effects of the acute and repeated administration of MK-801 on the release of adrenocorticotropin, corticosterone and prolactin in the rat

In addition to its producing profound changes in behavior, phencyclidine (PCP) disrupts neuroendocrine function in the rat. Because PCP binds to PCP as well as sigma receptors, it is not known which receptor type mediates the various effects of the drug. The purpose of the present study was to characterize the effects of the acute administration of enantiomers of MK-801, a compound with a high degree of selectivity for PCP over sigma receptors, on the release of ACTH, corticosterone and prolactin in the rat. In addition, MK-801 was administered daily for eight days in order to test whether tolerance develops to MK-801-induced ACTH and corticosterone release after repeated administration. While both enantiomers of MK-801 markedly increased plasma levels of ACTH and corticosterone, the (+) enantiomer was more potent. Tolerance developed to MK-801-induced increases in ACTH and corticosterone after repeated administration. Plasma prolactin levels were not affected by either the acute or the repeated administration of MK-801. These results suggest that the decrease in plasma levels of prolactin produced by PCP-like drugs is not mediated by PCP receptors, and may be a marker for a sigma receptor-mediated effect.     

Effects of repeated zimelidine administration on sleep parameters in the rat

The purpose of this study was to determine if non-pharmacological stimuli influence behavioral tolerance to haloperidol via striatal postsynaptic dopamine receptors. Rats received daily haloperidol and saline in two different environments for a period of 28 days. After this conditioning period half of the rats received haloperidol in the haloperidol-associated environment, whereas the other half received haloperidol in the saline-associated environment. All rats were tested for catalepsy and at the end of the last catalepsy test, striatal DOPAC, HVA and ACh were determined. Only the rats tested in the haloperidol-associated environment were behaviourally tolerant to haloperidol. In contrast, both groups were biochemically tolerant to haloperidol.These results indicate that environmental cue factors govern the development of behavioural tolerance to haloperidol, rather than biochemical factors (striatal DA supersensitivity). In addition, these factors do not exert their influence on behavioural tolerance via striatal DA receptors.     

Effect of chronic lead treatment on brain dopamine synthesis and serum prolactin release in the rat

The effect of chronic dietary lead exposure on brain striata dopaminergic transmission was studied in rats by measuring dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Serum prolactin (PRL) concentration was also measured. The results show a decreased striatal dopamine synthesis and increased serum PRL concentrations.     

Modulation by dopamine receptors of the histamine release in the rat hypothalamus

Summary The involvement of dopaminergic neurons of the hypothalamus in the modulation of histamine release was studied by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial cerebrospinal fluid (CSF) and the release of histamine was determined radioenzymatically in the superfusate. Agonists and antagonists of dopamine D₁-, D₂- and D₃-receptors were dissolved in CSF and applied to the hypothalamus through the push-pull cannula.Hypothalamic superfusion with the D₁-, D₂- and D₃-receptor agonists dopamine or R(–)-apomorphine enhanced the release rate of histamine. (±) Apomorphine also enhanced the release of histamine, but to a lesser extent than did equimolar concentration of R(–)apomorphine. The D₃-agonist quinpirole inhibited the release of histamine, while the D₁-receptor agonist SKF 82958 [(±)-6-chloro-7,8-dihydroxy-3-allyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] did not virtually influence the release of the neurotransmitter. On the other hand, [–]-sulpiride which predominantly blocks D₂-receptors, decreased histamine release. Hypothalamic superfusion with SKF 83566 [(±)-7-bromo-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], which seems to be a selective antagonist of D₁-receptors, enhanced the release rate of histamine.These findings suggest that dopaminergic neurons of the hypothalamus influence the release of histamine from its neurons in a dual way. D₂-heteroreceptors stimulate the release of histamine, while D₃-heteroreceptors seem to inhibit the release of this neurotransmitter. Both types of dopamine receptors might be located presynaptically on histaminergic neurons. Alternatively, D₃- and D₂-receptors might be located on histaminergic and non-histaminergic neurons, respectively.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung Correspondence to H. Prast at the above address     

Effect of sex steroids on GABA receptors in the rat hypothalamus and anterior pituitary gland

Our data indicate that sex steroids modify the number of GABA receptors, as detected by a [3H]muscimol binding assay, in the tuberoinfundibular GABAergic system. GABA binding was affected by chronic hormonal treatments in different ways depending on the sex of the rats and the steroids administered. Estradiol increased GABA binding in ovariectomized female rats while testosterone decreased the number of GABA binding sites in gonadectomized male rats. These results suggest a sex difference in the regulation of hypothalamic GABA receptors.     

Effect of repeated administration of manganese on the striatal cholinergic and dopaminergic receptors in the rat

Previous studies suggest that chronic administration of manganese produces symptoms akin to Parkinson's disease, which is believed to be due to derangement in the central cholinergic and dopaminergic system. In the present study the effect of repeated administration of manganese chloride to male Sprague-Dawley rats on the binding of [3H]spiroperidol and [3H]quinuclidinyl benzilate to striatal dopaminergic and cholinergic receptors, respectively, was determined. Daily intraperitoneal injections of manganese chloride (15 mg/kg) for 15 days followed by a 24 h drug-free period did not alter the receptor density (Bmax) or the apparent dissociation constant (Kd) of either [3H]spiroperidol or [3H]quinuclidinyl benzilate to the rat striatal membranes. It is concluded that chronic treatment with manganese does not change the plasticity of post-synaptic dopaminergic or cholinergic receptors in the rat striatum.     

Neurotransmitter effects on in vitro prolactin and growth hormone release from fowl pituitary glands: dopamine and noradrenaline

Pituitary glands and hypothalami from broiler fowl heads were incubated alone or together with dopamine, noradrenaline or monoaminergic drugs (apomorphine, pimozide, phentolamine, isoproterenol and propranolol). The basal release of both prolactin and growth hormone was not affected by any of these amines or aminergic drugs. The co-incubation of pituitary glands with whole hypothalami consistently stimulated prolactin and growth hormone secretion. Apomorphine inhibited hypothalamus-induced prolactin and growth hormone release and the response was blocked by pimozide. Noradrenaline markedly stimulated hypothalamus-induced prolactin release, an effect antagonised by phentolamine. Thyrotrophin-releasing hormone (TRH) stimulated the release of prolactin and this stimulation was reversed, in a dose-related manner, by dopamine. TRH also increased the release of growth hormone, in the presence or absence of dopamine. These results demonstrate inhibitory dopaminergic effects on prolactin and growth hormone secretion and stimulatory noradrenergic effects on prolactin release. These aminergic effects may be mediated at pituitary and/or hypothalamic sites.     

Effects of repeated morphine on cerebral dopamine release and metabolism in AA and ANA rats

Cerebral dopaminergic mechanisms were studied in the nucleus accumbens and caudate-putamen of alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Non-Alcohol) rats after 4-day repeated morphine treatment. This treatment has been shown to enhance the locomotor activity stimulating effect of morphine in the AA but not in the ANA rats. Morphine (1 or 3 mg/kg) or saline was administered subcutaneously once daily and the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured, in freely moving rats by in vivo microdialysis on days 1 and 4. Morphine increased accumbal DA, DOPAC and HVA similarly in rats of both lines, and no sensitization of DA release or metabolism was seen in rats of either line given morphine repeatedly. In the caudate-putamen, morphine increased DA, DOPAC and HVA significantly only in the AA rats. During repeated treatment, the morphine-induced elevation of DA metabolites, but not that of DA, was enhanced similarly in rats of both lines. These results suggest that the effects of acute morphine administration on nigrostriatal dopaminergic mechanisms are stronger in the AA than in the ANA rats, whereas the effects of morphine on mesolimbic dopaminergic systems do not differ. Furthermore, in rats of both lines, repeated morphine treatment enhanced the responses of the nigrostriatal dopaminergic systems similarly, but no enhancement occurred in the mesolimbic systems of rats of either line. These findings do not support the critical role of accumbal dopaminergic systems in morphine-induced behavioural sensitization.     

Effects of repeated nicotine administration and footshock stress on rat mesoprefrontal dopamine systems: Evidence for opioid mechanisms.

We have examined the effects of nicotine pre-treatment on mesoprefrontal dopamine (DA) function in the presence and absence of acute stress, and the involvement of endogenous opiate peptide systems (EOPS). Acute electrical footshock stress preferentially increases DA utilization in medial prefrontal cortex (mPFC) compared to nucleus accumbens (NAS) and striatal terminal fields, and this is correlated with profound locomotor immobility. Our recent studies have demonstrated that repeated, but not acute, nicotine pre-treatment significantly reduced mPFC DA utilization and footshock stress-induced immobility responses. There is increasing evidence that the biochemical and behavioral effects of nicotine are mediated by EOPS, and we hypothesized that the stress-reducing effects of repeated nicotine administration in these studies were mediated by EOPS. Accordingly, rats pre-treated subcutaneously with repeated nicotine were given a single dose of the opiate receptor antagonist naloxone (0.1-10.0 mg/kg, i.p.) or saline as a co-treatment with nicotine or saline 10 min prior to acute footshock stress. Naloxone had no effects on non-stressed or acute footshock stress-induced mPFC DA utilization, but dose-dependently antagonized repeated nicotine's attenuation of stress-induced mesoprefrontal DA utilization and immobility responses. Furthermore, naloxone dose-dependently blocked repeated nicotine's augmentation of accumbal DA utilization. These results suggest that EOPS may be involved in mediating repeated nicotine administration effects on mesoprefrontal dopaminergic and immobility responses to acute footshock stress.