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Biomedical subjects

R B Mailman

Publications and source records attributed to R B Mailman.

At least 127 records · Page 7Linked to original sources
PubMed1981

Effect of 5,7-dihydroxytryptamine on serotonergic control of prolactin secretion and behavior in rats.

The intracisternal administration of 5,7-dihydroxytryptamine (5,7-DHT) to rats resulted in a potentiated response to 5-hydroxytryptophan (5-HTP) when the animals were tested 30 days later. The 5-HTP-induced changes include elevation of serum prolactin, decrease in operant responding, and the magnitude of the "serotonin behavioral syndrome" observed after 5-HTP administration. The serotonin concentration in brains of 5,7-DHT-treated animals reached maximum earlier and remained elevated longer than that of controls following administration of 5-HTP. Brain norepinephrine and dopamine concentration were not affected by 5-HTP in either group of animals. The increase in serum prolactin concentration elicited by administration of the serotonergic agonists quipazine or 5-methoxy-N,N-dimethyltryptamine and by the serotonin uptake inhibitor fenfluramine also was potentiated by pretreating rats with 5,7-DHT. These data suggest that both serotonergic receptor supersensitivity and the absence of presynaptic uptake sites contribute to the enhanced responses to 5-HTP occurring in rats previously treated with 5,7-DHT. The findings further demonstrate that both behavioral and hormonal measures can be used to assess the sensitivity of serotonergic receptors and indicate that 5,7-DHT may be useful in evaluating the role of serotonergic neurons in neuroendocrine function.

5,7-Dihydroxytryptamine↗
PubMed1981

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.

Adenylyl Cyclases↗
PubMed1981

Differential effects of TRH, amphetamine, naloxone, and fenmetozole on ethanol actions: attenuation of the effects of punishment and impairment of aerial righting reflex.

The effects of four putative ethanol antagonists [thyrotropin releasing hormone (TRH), naloxone, d-amphetamine, and fenmetozole] on two distinct behavioral actions of ethanol were compared. TRH (20-40 mg/kg) reduced ethanol-induced impairment of the aerial righting reflex (ARR) but enhanced the ethanol-induced increase in punished drinking (anticonflict effect). Naloxone antagonized both actions of ethanol but only at high doses (20-60 mg/kg). Amphetamine (1-4 mg/kg) abolished the ethanol effect on punished drinking but did not alter its impairment of the ARR (1-8 mg/kg). Conversely, fenmetozole antagonized the ethanol impairment of the ARR (15-30 mg/kg) but not ethanol's anticonflict action. The inconsistent pattern of "antagonist" interactions of these drugs with the behavioral actions of ethanol suggests that ethanol alters several neurochemical systems to produce its behavioral effects.

Amphetamine↗
PubMed1981

Effects of TRH on central nervous system function.

Evidence has been reviewed which strongly suggests that TRH functions as a neurotransmitter or neuromodulator in the mammalian central nervous system. Both the peptide and its receptor sites are located in the brain. Furthermore, it has protein actions to modify the effects of many neuropharmacological agents and can itself cause alterations in functions mediated by the CNS. Data clearly indicate that many of these actions. of TRH are not dependent on the pituitary- thyroid axis. Various studies of neurotransmitter interactions with TRH have provided evidence that noradrenergic, serotonergic, GABAergic, and cholinergic systems may be influenced by TRH or mediate some of its actions. More than likely, other transmitters will be implicated as the complex actions of TRH are more thoroughly investigated and understood. One set of experiments suggested that TRH may be localized serotonergic fibers. Such findings provide strong support for the view that TRH has a role in the physiology of the CNS. In spite of the progress that has been made, there are several questions to be answered about mechanisms of synthesis, storage, release, and inactivation of TRH. Furthermore, physiological studies would be greatly facilitated if a specific antagonist of TRH actions were available. Controversy still exists about active forms of TRH in situ and the methods by which TRH can be measured in tissue. Future investigations which resolve these difficulties and questions should facilitate our understanding of the role of TRH in brain function and its complex interactions with other neural mechanisms.

Animals↗
PubMed1981

Effects of acute and chronic 1,3-butanediol treatment on central nervous system function: a comparison with ethanol.

In the present investigation, the neuropharmacology of 1,3 butanediol (1,3-BD) was compared with that of ethanol. Acute i.p. administration of equimolar doses of 1,3-BD or ethanol to rats impaired the aerial righting reflex, attenuated the suppressive effect of punishment on drinking behavior, lowered blood pressure, caused a concomitant reduction in the content of guanosine 3',5'-monophosphate in the cerebellum and reduced ethanol withdrawal reactions. Although these data suggested that ethanol and 2,3-BD were of similar potency, the brain content of 1,3-BD was only 33% of that of ethanol after treatment with equimolar doses, suggesting a greater central nervous system (CNS) potency for 1,3-BD. In rats treated chronically with ethanol to produce physical dependence, 1,3-BD was more potent than ethanol in inhibiting the hyperexcitability observed upon ethanol withdrawal. Furthermore, chronic administration and withdrawal of 1,3-BD caused CNS hyperexcitability in rats that was characteristic of physical dependence. Despite these similarities, there were clear differences in the actions of ethanol and 1,3-BD. In mice, locomotor stimulation caused by ethanol was not observed after 1,3-BD. Furthermore, while 1,3-BD did not alter the concentration of luteinizing hormone in plasma, equivalent doses of ethanol markedly reduced the concentration of this hormone. These data indicate that like ethanol, 1,3-BD depresses CNS activity and induces physical dependence, but has less effect on plasma luteinizing hormone concentration than ethanol.

Animals↗
PubMed1980

Erythrosine (Red No. 3) and its nonspecific biochemical actions: what relation to behavioral changes?

Biochemical studies have shown that the ability of erythrosine to inhibit dopamine uptake into brain synaptosomal preparations is dependent on the concentration of tissue present in the assay mixture. Thus, the finding that erythrosine inhibits dopamine uptake (which, if true, would provide a plausible explanation of the Feingold hypothesis of childhood hyperactivity) may simply be an artifact that results from nonspecific interactions with brain membranes. In addition, although erythrosine given parenterally (50 milligrams per kilogram) did not alter locomotor activity of control of 6-hydroxydopamine-treated rats, erythrosine (50 to 300 milligrams per kilogram) attenuated the effect of punishment in a "conflict" paradigm.

Animals↗
PubMed1980

An evaluation of the selectivity of fenmetozole (DH-524) reversal of ethanol-induced changes in central nervous system function.

The selectivity and specificity of fenmetozole (DH-524) [2(3,4-dichlorophenoxy-methyl)2-imidazole HCl] as an antagonist of the actions of ethanol were examined. Fenmetozole (15--30 g/kg) reduced ethanol-induced impairment of the aerial righting reflex without changing blood or brain ethanol content, indicating that the antagonistic actions of fenmetozole were not de to change in the pharmacokinetics of ethanol. Since fenmetozole also reduced aerial righting reflex impairment due to phenobarbital, chlordiazepoxide, and halothane, this action of fenmetozole was not specific to ethanol. In mice, both the ethanol-induced increase in locomotor activity at 2.0 g/kg and the decrease caused by 4.0 g/kg were antagonized by fenmetozole. In addition, fenmetozole attenuated the ethanol-induced reduction in cerebellar cyclic guanosine monophosphate (cGMP) content, but the drug also significantly elevated cGMP levels in this tissue when given alone. Fenmetozole did not alter ethanol-induced increases in punished drinking in a conflict test, except at a high dose which alone decreased both punished and unpunished responding. Fenmetozole also failed to precipitate ethanol withdrawal-like reactions when given to physically-dependent, intoxicated rats. Thus, the antagonistic action of fenmetozole against ethanol would not seem to be related to a specific receptor interaction but rather may be the result of a physiological antagonism.

Acoustic Stimulation↗
PubMed1980

Importance of the Locus coeruleus and involvement of alpha-adrenergic receptors in the post-decapitation reflex in the rat.

The latency, duration, hindlimb kick frequency, and total activity components of the post-decapitation reflex (PDR) were measured in the rat using a movement-sensitive transducer. Reduction of brain and spinal cord norepinephrine (NE) caused by neonatal administration of 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine, which also reduced brain serotonin, decreased all components of the PDR. Depletion of serotonin or dopamine alone reduced the vigor of the reflex, suggesting that these pathways can influence the PDR but are not essential for the response. Lesions of neurons in the Locus coeruleus, made electrolytically or with 6-OHDA, decreased the intensity of the PDR, with the 6-OHDA-induced lesion being more effective. Depletion of forebrain NE terminals with 6-OHDA did not alter the PDR, consistent with a critical involvement of spinal noradrenergic fibers. The PDR was also decreased by phentolamine and prazosin, but not by propanolol, suggesting an involvement of alpha-adrenergic receptors in the response. This hypothesis was further supported by the finding that the efficacy of a variety of drugs (such as tricyclic antidepressants, phenothiazines, and anti-hypertensive compounds) for blocking the reflex was apparently related to their affinity for alpha-adrenergic receptors. Thus, the PDR is dependent on noradrenergic fibers in the spinal cord and may provide a simple screen for drugs with suspected alpha-adrenergic blocking properties or for agents that disrupt the function of central noradrenergic fibers.

5,7-Dihydroxytryptamine↗
PubMed1980

Attenuation of the effects of punishment by ethanol: comparisons with chlordiazepoxide.

Ethanol (ETOH), like chlordiazepoxide (CDZ), significantly attenuated the suppressive effect of punishment on licking behavior in water-deprived rats and mice. In rats, the greatest effects of ETOH (1.5 g/kg) were observed between 30 and 60 min following IP administration. tert-Butanol also attenuated the effects of punishment, suggesting that acetaldehyde was not contributing to this effect of ETOH. Since a dose of ETOH that increased punished drinking did not increase unpunished drinking, alteration in thirst motivation would not appear to be responsible for its antipunishment action. However, doses of ETOH or CDZ that significantly increased punished responding increased jump thresholds to aversive shock, suggesting that decreased sensitivity to aversive stimulation may contribute to the anti-punishment action of both agents. In addition to these similarities between ethanol and CDZ, several differences were noted in their effects. For example, CDZ decreased serum corticosterone concentration, whereas ETOH did not. Further, ETOH impaired aerial righting reflex and reduced rectal temperature, whereas CDZ had no effect on these parameters at doses that had anti-punishment activity. Finally, specific binding of [3H]flunitrazepam to crude brain cortical membranes was decreased by CDZ, but not ETOH. Although ETOH and CDZ similarly alter punished behavior, results suggest that ETOH does not act through a direct interaction with a benzodiazepine binding site.

Animals↗
PubMed1979

Change in brain guanosine 3',5'-monophosphate (cGMP) content by thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) causes a significant increase in rat cerebellar guanosine 3',5'-monophosphate (cGMP) content after parenteral administration. A smaller but still significant increase in cGMP was also observed in brain stem, whereas no significant changes were observed in cGMP in other gross brain regions or in adenosine 3',5'-monophosphate in any brain region. TRH also caused a similar increase in cerebellar cGMP content in hypophysectomized rats indicating that the increase is independent of an intact pituitary. The time course of cGMP elevation in the cerebellum after administration of 10 mg/kg of TRH i.v. showed a peak at 2.5 to 5.0 min followed by a less rapid decrease. The time course of TRH immunoreactivity in the same cerebellar homogenates roughly paralleled these changes. Only those TRH analogs which were previously shown to antagonize pentobarbital sleeping time in mice caused an elevation in cGMP content in the cerebellum. TRH also caused a significant increase in cerebellar cGMP in rats pretreated with phenobarbital and chlordiazepoxide. The TRH-induced increase in cerebellar cGMP was not affected by cerebellar climbing fiber lesions caused by 3-acetylpyridine nor blocked by haloperidol, suggesting that TRH acts by mechanisms different from harmaline or apomorphine in raising cerebellar cGMP.

Animals↗