Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue

Ross, Svante B.; Renyi, A. L.

doi:10.1016/0014-2999(69)90091-0

Cited by 315 publications

(84 citation statements)

References 8 publications

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“…There is now good in vivo and in vitro evidence that tricyclic antidepressants having a tertiary amine function are more potent inhibitors of 5-HT uptake than those with a secondary amino group (Carlsson, Corrodi, Fuxe & Hokfelt, 1969;Ross & Renyi, 1969;Carlsson, 1970;Shaskan & Snyder, 1970: Lidbrink, Jonsson & Fuxe, 197 1; Kannengiesser, Hunt & Raynaud, 1973). The fact that the quaternary methyl amino compound of imipramine was twice as potent as the parent drug indicates that the active form of the terminal amino group at the uptake site is probably the positively charged species.…”

Section: Discussionmentioning

confidence: 99%

Structure‐activity Relations for the Inhibition of 5‐hydroxytryptamine Uptake by Tricyclic Antidepressants Into Synaptosomes From Serotonergic Neurones in Rat Brain Homogenates

Horn

Trace

1974

British J Pharmacology

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The inhibitory effects of various analogues of imipramine on [3H]‐5‐hydroxytryptamine (5‐HT) uptake into homogenates of rat hypothalamus were examined. For structures with a three carbon side chain the tertiary amine derivative was more potent than the compound with a secondary amine function. Potency was reduced by increasing or decreasing the length of the three carbon side chain by one carbon atom. Substitution of a methyl group in the α or β position in the side chain reduced potency. Replacement of the dimethylene bridge in imipramine by a sulphur atom or substitution of a C=C double bond for the exocyclic N‐C bond of imipramine both led to a fall in potency. 3‐Chlorimipramine was the most potent inhibitor of [3H]‐5‐hydroxytryptamine uptake of the compounds tested.

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Section: Discussionmentioning

confidence: 99%

Structure‐activity Relations for the Inhibition of 5‐hydroxytryptamine Uptake by Tricyclic Antidepressants Into Synaptosomes From Serotonergic Neurones in Rat Brain Homogenates

Horn

Trace

1974

British J Pharmacology

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“…The main pharmacological effect of cocaine is to inhibit the reuptake of monoamines dopamine, norepinephrine, and serotonin at presynaptic terminals. As a consequence of these ac- (Hadfield et al 1980;Heikkila et al 1975;Ross and Renyi 1969). The major behavioral effect of cocaine is a psychomotor stimulant action with reinforcing addictive properties.…”

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confidence: 99%

Extinction of Cocaine Self-Administration Produces a Differential Time-Related Regulation of Proenkephalin Gene Expression in Rat Brain

Crespo

Manzanares

Martínez

et al. 2001

Neuropsychopharmacology

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The purpose of this study was to examine the time course effects of extinction of cocaine self-administration behavior on proenkephalin (PENK) gene expression in caudateputamen nucleus (ST), nucleus accumbens (Acc), olfactory tubercle (Tu), piriform cortex (Pir), ventromedial hypothalamic nucleus (VMN), and central amygdala (Ce) as measured by in situ hybridization histochemistry. Seventy-two littermate male Lewis rats were randomly assigned in triads to one of three conditions: (1) contingent intravenous self-administration of 1 mg/kg/injection of cocaine (CONT); (2) noncontingent injections of either 1 mg/kg/injection of cocaine (NONCONT); or (3) saline yoked (SALINE) to the intake of the self-administering subject. The self-administering rats were trained to selfadminister cocaine under a FR5 schedule of reinforcement for a minimum of 3 weeks. After stable baseline levels of drug intake had been reached, saline was substituted for drug. Following this first extinction period, cocaine selfadministration was reinstated for an additional period of 2 weeks. Immediately after cessation of the last session of cocaine self-administration (day 0) and 1-, 5-, and 10-day after the second extinction period, animal brains in eachCocaine abuse and dependence remain major public health and social problems. Cocaine abuse results from a complex interplay of behavioral, pharmacological, and neurobiological determinants. The main pharmacological effect of cocaine is to inhibit the reuptake of monoamines dopamine, norepinephrine, and serotonin at presynaptic terminals. As a consequence of these ac- (Hadfield et al. 1980;Heikkila et al. 1975;Ross and Renyi 1969). The major behavioral effect of cocaine is a psychomotor stimulant action with reinforcing addictive properties. This behavioral effect is produced primarily by inhibition of dopamine uptake, thereby increasing extracellular concentrations of released dopamine (Ritz et al. 1987; for a review see Kuhar et al. 1991;Spanagel and Weiss 1999). However, a recent study using mice lacking dopamine transporter proposed other mechanisms, such as increases in serotonin transmission, may mediate the reinforcing effects of cocaine (Rocha et al. 1998).Several studies have shown that cocaine also affects the expression of opioid peptides and opioid receptors. For example, chronic cocaine administration leads to increases in circulating ␤ -endorphin levels (Moldow and Fischman 1987), striatal preprodynorphin mRNA levels (Hurd et al. 1992;Daunais et al. 1993;Daunais and McGinty, 1995;Spangler et al. 1993Spangler et al. , 1996Spangler et al. , 1997, and striatonigral dynorphin content (Sivam 1989;Smiley et al. 1990) in rats and to decreases in preproenkephalin mRNA levels in rhesus monkeys (Daunais et al. 1997) and humans (Hurd and Herkenham 1993). Repeated administration of cocaine can also regulate the activity of opioid receptors in discrete brain regions of rats. Indeed, it has been shown that 2 weeks of either continuous administration of cocaine via subcutaneously implanted osmotic...

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“…Knapp & Mandell (1972) have shown that cocaine in vitro decreased 5-HT synthesis by inhibition of tryptophan uptake and not by direct inhibition of tryptophan hydroxylase. However, inhibition of synthesis, especially in the presence of the blockade of 5-HT uptake known to be an effect of cocaine (Ross & Renyi, 1969), would be expected to result in a precipitous fall in brain 5-HT levels. Our finding of only a slight decrease in brain 5-HT concentrations suggests that cocaine also inhibits the release and/or metabolism of 5-HT.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute Cocaine Treatment on the Turnover of 5‐hydroxytryptamine in the Rat Brain

Friedman

Gershon

Rotrosen

1975

British J Pharmacology

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I The effects of cocaine (20 mg/kg s.c.) on 5-hydroxytryptamine (5-HT) turnover were examined in rats. 2 In vivo cocaine administration resulted in decreased turnover of 5-HT, as indicated by the decreased accumulation of 5-HT after pargyline administration and the decreased accumulation of 5-hydroxyindoleacetic acid (5-HIAA) following probenecid injection. 3 A time-related decrease in 5-HIAA concentrations and a small fall in 5-HT concentrations in the whole brain were observed following the acute administration of cocaine hydrochloride (20 mg/kg). Tryptophan levels were found to be slightly decreased in the brain. 4 Enhanced reactivity, but neither stereotypy nor hyperthermia, was observed following cocaine injection (20 mg/kg). 5 It is concluded that cocaine inhibits the turnover of brain 5-HT and that this action of cocaine may be responsible for the differences in a number of pharmacological effects between cocaine and amphetamine.

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Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue

Cited by 315 publications

References 8 publications

Structure‐activity Relations for the Inhibition of 5‐hydroxytryptamine Uptake by Tricyclic Antidepressants Into Synaptosomes From Serotonergic Neurones in Rat Brain Homogenates

Structure‐activity Relations for the Inhibition of 5‐hydroxytryptamine Uptake by Tricyclic Antidepressants Into Synaptosomes From Serotonergic Neurones in Rat Brain Homogenates

Extinction of Cocaine Self-Administration Produces a Differential Time-Related Regulation of Proenkephalin Gene Expression in Rat Brain

Effects of Acute Cocaine Treatment on the Turnover of 5‐hydroxytryptamine in the Rat Brain

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