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PubMed1983

Changes in responsiveness of the beta-adrenergic and serotonergic pathways of the rabbit corneal epithelium.

Adrenergic agonists stimulate the synthesis of cyclic AMP by incubated rabbit corneas with the following order of potency: isoproterenol greater than epinephrine greater than norepinephrine. These agonists have the same order of potency when displacing the specific, beta-adrenergic radioligand, 3H-dihydroalprenolol, from beta-adrenergic receptors on membranes prepared from corneal epithelium. At another locus, serotonin stimulates cyclic AMP synthesis. Inhibition of stimulation in vitro by lysergic acid diethylamide, methysergide, cyproheptadine, and spiroperidol demonstrates the specificity of this pathway for serotonin. Topical epinephrine causes subsensitivity or decreased responsiveness of the beta-adrenergic pathway. There is loss of approximately half the beta-adrenergic receptors from the cornea and a similar loss of epinephrine-stimulated cyclic AMP synthesis, both of which return to control levels in 96 hrs. There is no change in affinity for catecholamines and no loss of responsiveness to prostaglandin E2 or serotonin. Pretreatment with nialamide or subsequent treatment with additional epinephrine does not cause further loss of responsiveness. Supersensitivity or increased responsiveness of this pathway occurs following superior cervical ganglionectomy. Topical serotonin causes decreased responsiveness of the serotonergic pathway. When potentiated by nialamide, serotonin causes almost complete loss of serotonin-stimulated cyclic AMP synthesis for 24-48 hrs. There is no loss of responsiveness to epinephrine. Increased responsiveness of this pathway does not occur following superior cervical ganglionectomy. The authors conclude that the corneal epithelium has both beta 2-adrenergic and serotonin-2 pathways, and each pathway exhibits altered responsiveness by similar mechanisms. In response to exogenous or endogenous stimulation, the beta-adrenergic responsive cells and the serotonergic responsive cells apparently regulate the total number of pathway-specific receptors on their surfaces. Furthermore, the authors postulate that two populations of beta-adrenergic responsive cells exist; those on the apical surface of the epithelium that respond to catecholamine in the tears and those near the basal surface that respond to neuronal catecholamine.

Adrenergic beta-Agonists↗
PubMed1984

Receptor autoradiography in thoracic spinal cord: correlation of neurotransmitter binding sites with sympathoadrenal neurons.

Receptor autoradiography was combined with the retrograde labeling of sympathoadrenal neurons by fast blue to determine whether opiate, serotonin, catecholamine, or cholinergic binding sites could be spatially correlated with preganglionic neurons in the rat intermediolateral cell column (IML) that project to the adrenal gland. [3H]Dihydromorphine (DHM) was used for the visualization of mu opiate receptors, [3H]lysergic acid diethylamide (LSD) for serotonin receptors, [3H]para-aminoclonidine (pAC) for alpha 2-adrenergic receptors, and [3H]quinuclidinyl benzilate (QNB) for muscarinic cholinergic receptors. While qualitative assessment of autoradiograms indicated that alpha 2-adrenergic and muscarinic receptors were concentrated in the intermediate zone of the spinal cord, quantitation of grains in specific regions of the intermediate gray revealed that alpha 2-adrenergic and serotonergic receptors were more highly concentrated over sympathoadrenal preganglionic neurons than over other regions in IML or the adjacent intermediate gray matter. Information concerning the distribution of neurotransmitter-binding sites in other regions of thoracic spinal cord was also obtained. All ligands showed relatively dense binding sites in the superficial laminae of the dorsal horn, and all but [3H]DHM revealed similar densities of binding sites in the region adjacent to the central canal. Only [3H]QNB revealed a high density of binding sites in the ventral horn of the spinal cord.

Adrenal Medulla↗
PubMed1982

Neural serotonin stimulates chloride transport in the rabbit corneal epithelium.

Evidence is presented that serotonin acts as a neurotransmitter in the cornea of the adult rabbit. Serotonin was localized to granules in a sparse population of subepithelial corneal nerves by an electron microscopic histochemical procedure. Significant endogenous levels of serotonin and its principal metabolite, 5-hydroxyindoleacetic acid, were detected in the central cornea by a fluorometric assay. Exogenous serotonin stimulated ion transport by corneal epithelium. This effect was potentiated by monoamine oxidase inhibition and was unaffected by an alpha-adrenergic receptor antagonist. Serotonin-stimulated ion transport was inhibited by the specific antagonist, methysergide, and by the replacement of Cl- with an impermeable anion. In tracer experiments, the serotonin-stimulated ion transport was shown to be caused by increased epithelial Cl- secretion. The serotonin response was partially inhibited by the beta-adrenergic antagonist, timolol. In a companion article, assay of corneal cyclic AMP showed stimulation of cyclic AMP synthesis by serotonin, inhibition by the specific antagonist, lysergic acid diethylamide, and potentiation by monoamine oxidase inhibition. We postulate that specific serotonergic receptors are present in the corneal epithelium and that activation of these receptors by serotonin released from serotonergic neurons increases the level of cyclic AMP, which stimulates active Cl- secretion by the corneal epithelium.

Animals↗
PubMed1978

Effects of d-amphetamine, monomethoxyamphetamines and hallucinogens on schedule-controlled behavior.

The effects of 16 drugs were studied in rats responding under fixed-ratio (FR 30) and fixed-interval (FI 2 minute) schedules of food presentation. The drugs tested included lysergic acid diethylamide (LSD), dimethyltryptamine, mescaline, d-amphetamine and 12 methoxylated amphetamines. All of the drugs decreased the average rates of responding under both schedules, but their potencies varied widely. For example, with LSD, the most potent drug tested, doses of 0.1 to 0.3 mg/kg were sufficient to reduce responding while with dimethyltryptamine and mescaline, doses of 10 to 30 mg/kg were required to clearly reduce responding. For the 12 drugs which are known to produce hallucinogenic effects, their potencies in reducing responding were positively correlated with their reported potencies in producing these subjective effects in humans. Although all of the drugs decreased the average rates of responding, alterations in the patterns of responding under the FR and FI schedules varied among the drugs. Analysis of responding under the FI schedule indicated that d-amphetamine, m-methoxyamphetamine, p-methoxyamphetamine, LSD and 3,4-methylenedioxyamphetamine generally increased the low rates of responding occurring at the beginning of each interval and decreased the high rates of responding occurring later in each interval (rate-dependent effects). The other drugs generally decreased responding throughout the interval. These results are discussed in terms of the known neurochemical effects of these drugs.

Amphetamines↗
PubMed1981

Analysis of the cerebrovascular effects of 5-hydroxytryptamine in unanesthetized goats.

The effects of 5-hydroxytryptamine (5-HT, serotonin) on cerebral blood flow were evaluated in unanesthetized goats under normal conditions and after selective blockade of 5-HT receptors or impairment of the sympathetic activity present in cerebral vessels. Small doses of 5-HT (0.1-9 micrograms) injected directly into the internal maxillary artery produced dose-dependent reductions in cerebral blood flow, a decrease of 49.8 +/- 2.5% (S.E.M.) occurring with the highest dose. Slow i.v. infusion of lysergic acid diethylamide (0.2-0.4 micrograms/kg/min), methysergide or cyproheptadine (2-5 micrograms/kg/min) partially abolished the cerebral vasoconstriction produced by 5-HT. Both phentolamine and reserpine also diminished the vasoconstriction induced by 5-HT. Goats in which the superior cervical sympathetic ganglion had been removed 7 to 20 days before the experiment showed a significant decrease in the cerebral vasoconstriction elicited by 5-HT. These results indicate that 5-HT produces marked reduction in cerebral blood flow by direct excitatory effect on tryptaminergic receptors together with an indirect effect mediated by the uptake of 5-HT into the sympathetic nerve endings and the release of norepinephrine.

Animals↗
PubMed1984

Pharmacological characterization of dopamine autoreceptors in the rat ventral tegmental area: microiontophoretic studies.

Extracellular single-cell recording and microiontophoretic techniques were used to characterize the presynaptic dopamine (DA) receptors (autoreceptors) on A10 DA neurons in the rat ventral tegmental area. Thus, the ability of various agonists to inhibit the activity of A10 DA neurons was compared. DA and the DA agonists N-n-propylnorapomorphine (NPA), apomorphine, lisuride, pergolide, LY141865 and bromocriptine all suppressed the activity of A10DA neurons. NPA was the most potent exogenous agonist, exerting effects that were similar to an equimolar concentration of DA (0.01 M). When ejected at equimolar concentrations (0.01 M) and equivalent ejection currents, the rank order of potency for these agonists was DA = NPA greater than LY141865 greater than pergolide = lisuride = apomorphine greater than norepinephrine greater than bromocriptine. The alpha-2 adrenoceptor agonist clonidine, the beta adrenoceptor agonist isoproterenol, the D-1 specific DA agonist SKF 38393 and the hallucinogenic ergot lysergic acid diethylamide exerted only weak effects or were inactive. The D-2 specific DA antagonist sulpiride completely blocked the rate-suppressant effects of DA and DA agonists but not those of gamma-aminobutyric acid. The purported D-1 specific DA antagonist SCH 23390 failed to block the effects of either DA or the D-2 specific DA agonist LY141865. These results indicate that DA agonists suppress the activity of the majority of A10 DA neurons by acting directly on somatodendritic DA autoreceptors which exhibit the pharmacological characteristics of D-2 receptors.

Animals↗
PubMedDate not supplied

Commerce in drugs and chemicals and the detection of clandestine laboratories.

There were 225 clandestine laboratories seized in the United States of America in 1982, an increase of 23 per cent over 1981. These laboratories most commonly produced methamphetamines, phencyclidine (PCP), lysergic acid diethylamide (LSD), amphetamine and methaqualone. In order to determine whether a seized drug has been clandestinely manufactured and to identify the source of the drug, special techniques are used, involving detailed physical and chemical examinations. The results of such examinations are computerized and compared with reference samples to provide indications of the drug source. Undercover techniques are also effectively used for the detection of clandestine laboratories. Chemicals necessary for the illegal production of drugs of abuse were often diverted from legitimate sources through international commerce, which, together with clandestine laboratories, are recognized as an international problem that requires monitoring through international co-operation.

Chemistry, Pharmaceutical↗
PubMed1984

Multiple states of the 5-hydroxytryptamine1 receptor as indicated by the effects of GTP on [3H]5-hydroxytryptamine binding in rat frontal cortex.

In several monoamine receptor systems, agonist but not antagonist binding is found to be associated with both a high- and a low-affinity state of the receptor. Guanine nucleotides, like GTP, can eliminate the high-affinity receptor state such that only the low-affinity state of the receptor is present. Since [3H]5-hydroxytryptamine ([3H]5-HT) is an agonist, its binding may also be associated with multiple states of a receptor. To evaluate this, the binding of [3H]5-HT to rat frontal cortical membranes was measured in the absence and presence of GTP. Three different types of binding experiments were performed: (a) saturation experiments, (b) dissociation experiments, and (c) competition experiments with 5-hydroxytryptamine (5-HT) agonists. When all three types of binding experiments were carried out in the absence of GTP, results from either graphical representations or computer analysis of the data indicated that a two-component model of binding described the data better than a single-component model. By contrast, in the presence of GTP, a one-component model adequately described the data obtained from either saturation or dissociation experiments. Competition of [3H]5-HT (15 nM) binding by three 5-HT agonists (5-methoxytryptamine, 5-HT, and d-lysergic acid diethylamide) was adequately described by a single-component system in the presence of GTP as well, even though all three agonists produced biphasic inhibition curves in the absence of the guanine nucleotide. These experimental results are consistent with the idea that the binding of [3H]5-HT in the absence of GTP is associated with multiple receptor states. Since the presence of multiple states can confound the interpretation of inhibition curves of [3H]5-HT binding caused by agonists, it is important to eliminate the high-affinity state of the receptor by including GTP in the binding assay.

Animals↗
PubMed1981

RX 336-M, a new chemical tool in the analysis of the quasi-morphine withdrawal syndrome.

RX 336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno-1',2',8',14 codeinone) and four other chemically-diverse agents--AG-3-5 (1-[2-hydroxyphenyl]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), Sgd 8473 (alpha-[4-chlorobenzylideneamino)-oxy]-isobutyric acid), thyrotropin releasing hormone (TRH), and sodium valproate--each induce signs of withdrawal, most notably 'wet-dog' shaking, after acute i.p. administration in drug-naive rats. They are therefore additions to a recently recognized and, as yet, ill-defined class of behaviorally active compounds. The pharmacological baselines that link these disparate agents together have been studied in the present work, using 'wet-dog' shaking as the behavioral measure and RX 336-M as the reference shake-inducing compound. Peripheral administration of clonidine, haloperidol, d-lysergic acid diethylamide, or morphine suppressed chemically induced shaking: naloxone had no marked effect. Reverse tolerance was associated with TRH-induced shaking whereas tolerance occurred with the other four compounds. Cross-tolerance interactions were asymmetrical. Thus, rats rendered tolerant to RX 336-M were cross-tolerant to AG-3-5, TRH, and sodium valproate but not to Sgd 8473; in contrast, RX 336-M-induced shaking was only significantly reduced in rats made tolerant to Sgd 8473. In view of the unidirectional nature of the cross-tolerance relationships studied, it is concluded that AG-3-5, Sgd 8473, sodium valproate, and TRH initiate 'wet-dog' shaking through neural substrates that differ from the one(s) associated with RX 336-M. Nevertheless, all five compounds may eventually trigger a common shake-inducing mechanism.

Animals↗
PubMed1981

Serotonin autoreceptors on dorsal raphe neurons: structure-activity relationships of tryptamine analogs.

A series of indole-ethylamines were tested for their ability to suppress the spontaneous firing of single dorsal raphe serotonergic neurons in the rat. The compounds were all derivatives of either tryptamine or N,N-dimethyltryptamine possessing hydroxy or methoxy substituents on the benzene ring portion of the indole nucleus. Their activity was assessed using quantitative microiontophoresis or following systemic (intravenous) administration. The serotonin autoreceptor or so-called "S2 receptor" mediating the inhibition of raphe serotonergic neurons was found to exhibit a high degree of structural specificity among the closely related tryptamine analogs. The following structure-activity rules were demonstrated: (1) for either hydroxy or methoxy derivatives, the relative favorability of the ring positions conforms to the series 5 much greater than 4 greater than 6; (2) methoxy derivatives are more sensitive to a shift of the ring substituent from the 5- to the 4- or 6-positions than are hydroxy compounds; and (3) activity is enhanced by N,N-dimethylation. Furthermore, addition of a methyl group at the 7-position of 5-methoxy-N,N-dimethyltryptamine markedly reduces the activity of this potent agonist. Of the radioligands which label brain serotonin receptors, the pharmacological characteristics of D-[3H]lysergic acid diethylamide binding best correspond to those displayed by the S2 receptor as determined in the present physiological analysis, although sufficient data are not yet available to make a complete comparison.

Animals↗
PubMed1983

Pharmacological evaluation of N-allynormetazocine (SKF 10,047) on the basis of its discriminative stimulus properties in the rat.

The purpose of the present experiments was to evaluate the pharmacological properties of the discriminative stimulus effects of the prototypic sigma receptor agonist N-allylnormetazocine (NANM, SKF 10,047). Rats were trained to discriminate between saline and 3.0 or 5.6 mg/kg of NANM in a two-choice, shock-avoidance procedure. NANM-like stimulus control of behavior was produced by the opiates, in order of relative molar potency, cyclazocine greater than NANM greater than N-propylnormetazocine HCI greater than levallorphan greater than dextrorphan greater than pentazocine. Metazocine produced NANM-like discriminative effects but only when tested concomitantly with naloxone. Seven other opiate derivatives, including levorphanol, ethylketazocine and nalorphine, failed to produce NANM-like discriminative stimuli. Among enantiomeric pairs tested in the lower training dose group, d-NANM and l-NANM as well as levallorphan and dextrallorphan were equipotent, but the levo isomers of cyclazocine and pentazocine were more potent than their dextro counterparts, whereas dextrorphan but not levorphanol produced NANM-like discriminative stimuli. In the lower training dose group, the opioid antagonist naloxone failed to antagonize the NANM-like discriminative effects of NANM, l-cyclazocine and levallorphan, although naloxone did produce a parallel shift to the right of the dose-effect curve for pentazocine, and "unmasked" NANM-like effects of higher doses of metazocine. The nonopiate psychoactive drugs phencyclidine and dexoxadrol, but not its enantiomer levoxadrol produced NANM-like discriminative stimuli. Propranolol also occasioned an appreciable percentage of NANM-appropriate responding in the lower training dose group but not the higher dose group. Diazepam, d-amphetamine, d-lysergic acid diethylamide tartrate, imipramine, clonidine and haloperidol also failed to produce NANM-like discriminative stimuli in the lower training dose group. The present results demonstrate that the discriminative stimulus properties of NANM are distinguishable from those of morphine and ethylketazocine but similar to those of dissociative anesthetics such as phencyclidine and lend additional support to the hypothesis that sigma receptors mediate the common actions of NANM and phencyclidine.

Animals↗
PubMed1982

Characterization of solubilized serotonin (S2) receptors in rat brain.

[3H]Spiperone binding sites were solubilized from rat frontal cortex and striatum by means of the mild detergent, lysolecithin. In the frontal cortex, the binding sites were extracted from a microsomal membrane fraction which was found to be enriched in serotonin (S2) receptors when labeled either with [3H]spiperone or with [3H]lysergic acid diethylamide. Although the extraction yield was relatively low, the [3H]spiperone binding sites solubilized from the frontal cortex retained the high-affinity characteristics of serotonin (S2) receptors in the original membrane: low KD (1.4 nM); binding saturable, reversible, and stereospecific; and displaying a high affinity toward the most potent serotonin antagonists (pirenperone, pipamperone, ketanserin, methysergide, and mianserin). There was a very good correlation between the drug potencies in both soluble and membrane preparations. The molecular dispersion of the soluble extract was assessed by several criteria, including a low sedimentation coefficient in sucrose gradient. No specific binding sites could be extracted from the cerebellum. In contrast, few binding sites endowed with the characteristics of serotonin (S2) receptors were detected in lysolecithin extracts from rat striatum. However, the S2 sites became more apparent when a tetralin derivative was added to the incubation medium in order to prevent [3H]spiperone binding on solubilized dopamine receptors. In contrast, when microsomal membranes from rat striatum were treated with digitonin, the solubilized [3H]spiperone binding sites were only of a dopaminergic nature.

Animals↗
PubMed1981

Chloroquine psychosis: a chemical psychosis?

Psychotic states are mimicked by the use of many drugs including amphetamines, cannabis, lysergic acid diethylamide, psilocybin, mescaline, isoniazid, and L-dopa. A paranoid psychotic picture in a clear sensorium is characteristic of amphetamine psychosis. In developing countries, malaria among other diseases is a frequent indicator of chloroquine administration. The present communication reports a series of chloroquine-induced psychosis in a clear sensorium simulating affective illness, such as mania, mixed affective states, or depression. The psychosis disappeared after cessation of the drug, combined with or without the use of low dosage phenothiazines in excited patients. From our cases, two types of presentation of chloroquine psychosis could be seen: (1) psychic with clear sensorium, mood changes, alteration in motor activity, delusions, and hallucinations; and (2) psycho-organic with clouded sensorium, disorientation, and fleeting hallucinations. The precise nature of the mechanism of the psychosis is not clear because of the limited number of reported cases.

Adolescent↗
PubMed1980

Reserpine abolishes movement-correlated atropine-resistant neocortical low voltage fast activity.

Following a large dose of atropine, rats display large amplitude slow waves in the neocortex during immobility, tremor, tooth-chattering and face-washing (Type II behavior) but display low voltage fast activity (LVFA) during walking, struggling, postural changes and head movement (Type I behavior). Rats treated with a large dose of reserpine usually continue to display LVFA during immobility as well as during movement although large amplitude slow waves are present more frequently than normal. A combination of reserpine and atropine abolishes all LVFA even during intense sensory stimulation or electrical stimulation of the reticular formation. Chlorpromazine, lysergic acid diethylamide, methysergide, phenoxybenzamine, pimozide, promethazine, propranolol and trifluoperazine do not have this effect when combined with atropine. In rats treated with nialamide prior to reserpine and atropine, LVFA continues to occur in association with Type I behavior just as in rats given atropine alone. It is proposed that the occurrence of LVFA in the neocortex is determined by two distinct reticulocortical systems. A cholinergic system produces all LVFA occurring during Type II behavior and a second system, dependent on a monoamine, produces LVFA in association with Type I behavior. The view that LVFA is a correlation of arousal or the sleep-waking cycle is criticized.

Animals↗
PubMed1995

Determination of the role of the 5-ht6 receptor in the rat brain: a study using antisense oligonucleotides.

The purpose of the present study was to determine possible physiological functions of the 5-ht6 receptor using antisense oligonucleotides (AOs) in male rats. Repeated intracerebroventricular treatment with AOs but not with a scrambled form of the antisense sequence (SO) gave rise to a specific behavioral syndrome of yawning, stretching and chewing and caused a 30% reduction in the number of [3H]-lysergic acid diethylamide binding sites (measured in the presence of 300 nM spiperone). Neither sequence, however, had any effect on other parameters measured (e.g., locomotor activity, body weight, food intake, body temperature and nociception). The specific behavioral syndrome did not appear to be caused by modulation of dopaminergic neurotransmission since no changes in the tissue levels of either dopamine or its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were seen. Furthermore, haloperidol (0.03 mg/kg s.c.) did not reduce the number of yawns or stretches. An increase in cholinergic neurotransmission did appear to be involved since the behavioral syndrome was dose-dependently antagonized by atropine. The present study suggests that 5-ht6 receptors are functionally expressed in the rat brain, where one of their functions appears to be the control of cholinergic neurotransmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Comparing the subjective, psychomotor and physiological effects of intravenous butorphanol and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of butorphanol in healthy nondrug-abusing volunteers and to compare and contrast the effects of butorphanol to those of morphine. Into an antecubital vein, the subjects (seven men and five women), who had no history of opiate dependence, were injected with 0, 0.5, 1.0 or 2.0 mg/70 kg of butorphanol or 10 mg/70 kg of morphine; a randomized, double-blind, crossover design was used. The subjective effects of butorphanol included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and Lysergic Acid Diethylamide scale of the Addiction Research Center inventory; increased visual analog scale ratings of "sedated," "coasting or spaced out" and "difficulty concentrating;" increased adjective checklist ratings of "sweating," "skin itchy" and "sleepy;" and increased "feel drug effect" and drug-liking ratings. Morphine had some subjective effects of a magnitude similar to those of an equianalgesic dose of butorphanol (2 mg) (e.g., "strength of drug effect," "sedated," "heavy or sluggish feeling" and "high"). However, other effects of morphine were lesser in magnitude (e.g., "coasting or spaced out," "drunken" and "lightheaded") than those of butorphanol. Also, morphine did not affect a number of ratings that were affected by butorphanol (e.g., "confused," "dreamy," "stimulated," "difficulty concentrating," "floating" or "sweating"). The psychomotor impairing effects of butorphanol, as measured by the Maddox Wing test, an eye-hand coordination test, and the Digit Symbol Substitution Test, were dose related; in contrast, morphine had no effect on psychomotor functioning. Both butorphanol and morphine induced miosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A dose-response analysis of the subjective, psychomotor and physiological effects of intravenous morphine in healthy volunteers.

The purpose of this study was to characterize the subjective, psychomotor and physiological effects of morphine in healthy volunteers. Subjects (10 males and 2 females) without histories of opiate dependence were injected in an antecubetal vein with 0, 2.5, 5.0 or 10 mg/70 kg of morphine, by using a randomized, double-blind, cross-over design. Subjective effects, psychomotor performance and physiological measures were assessed immediately before the injection and for up to 5 hr afterward. Morphine increased the Pentobarbital-Chlorpromazine-Alcohol Group, Amphetamine, the Lysergic Acid Diethylamide and the Morphine-Benzedrine Group scores and decreased Benzedrine Group scores on the Addiction Research Center Inventory. Increased visual analog scale ratings of "stimulated," "high," "sedated," "coasting or spaced out" and "drunken" were also obtained. On an opiate adjective checklist, subjects reported increased ratings of "flushing," "dry mouth" and "tingling." Drug liking was not significantly altered by morphine, but there was substantial intersubject variability with this measure. Some aspects of psychomotor performance (reaction time, Digit Symbol Substitution Test and Maddox Wing) were impaired by morphine; however, eye-hand coordination was not. Miosis was induced by morphine. Most effects of morphine were dose-related, some effects peaked soon after morphine injection (e.g., increased stimulated and high ratings) and dissipated gradually, whereas other effects did not peak until later into the session (sedation or exophoria). Our results are fairly consistent with other studies examining morphine effects in healthy volunteers, and also indicate that the profile of morphine effects differ between healthy volunteers and those with a history of opiate dependence.

Adult↗
PubMed1993

Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization.

Serotonin [5-hydroxytryptamine (5-HT)] is a neuromodulator that mediates a wide range of physiological functions by activating multiple receptors. Using a strategy based on amino acid sequence homology between 5-HT receptors that interact with guanine nucleotide-binding proteins, we have isolated from a mouse brain library a cDNA encoding a new serotonin receptor. Amino acid sequence comparisons revealed that this receptor was a close relative of the previously identified 5-HT5 receptor but was distant from all other 5-HT receptor subtypes; we therefore named it 5-HT5B. When expressed in COS-7 cells, the 5-HT5B receptor displayed a high affinity for the serotonergic radioligand 125I-lysergic acid diethylamide. Its pharmacological profile was distinct from that of all classic 5-HT receptor subtypes. However, the high affinity of the 5-HT5B receptor for 5-carboxamidotryptamine and its low affinity for sumatriptan indicated that it might correspond to recently described 5-HT1D-like binding sites that were labeled with [3H]5-carboxamidotryptamine and insensitive to sumatriptan. In situ hybridization experiments revealed that the 5-HT5B mRNA was expressed predominantly in the habenula and in the CA1 field of the hippocampus. We also determined the chromosomal localization of the 5-HT5A and 5-HT5B genes and of their human counterparts. The 5-HT5A gene colocalized with the mouse mutation reeler and the human mutation holoprosencephaly type 3, which both result in abnormal brain development, raising the possibility that the 5-HT5A receptor plays a role in brain development.

Amino Acid Sequence↗