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  • 1
    Electronic Resource
    Electronic Resource
    THE RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY IN THE RAT (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 11 (1984), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The relationship between left ventricle-to-body weight ratio (LV/BW), mean arterial pressure (MAP, the average of 12 h of intra-arterial monitoring in conscious animals) and plasma renin activity (PRA) was assessed at 12 weeks after unilateral clipping or sham operation in twenty-four one-kidney rats and twenty-six two-kidney rats.2. The degree of hypertension and left ventricular hypertrophy were similar in one-kidney and two-kidney groups. There was a close linear relationship between LV/BW and MAP which was similar in one-kidney and two-kidney rats.3. PRA was significantly elevated only in two-kidney rats and was not related to the degree of hypertrophy after accounting for the effect of PRA on MAP.4. These data suggest that activation of the renin-angiotensin system does not contribute directly to myocardial hypertrophy in rats with renal-clip hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1984.tb00291.x
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  • 2
    Electronic Resource
    Electronic Resource
    Enhancement of 5-HT-induced anorexia: a test of the reversibility of monoamine oxidase inhibitors (1989)
    Springer
    Psychopharmacology 98 (1989), S. 265-268 
    Details
    ISSN: 1432-2072
    Keywords: Clorgyline ; Reversible MAO inhibitors ; 5-HT ; Sucrose intake ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Subcutaneous injection of 1 mg/kg 5-hydroxytryptamine (5-HT) reduced the intake of a 10% sucrose solution in rats. A single injection of the monoamine oxidase inhibitor (MAOI) clorgyline enhanced the anorectic effect of 5-HT. Such an effect persists 2, 24, 48, 72 and 96 h after injection. The clorgyline treatment almost completely inhibited type A MAO activity in the liver at 2 h post-injection. By 120 h, the time at which potentiation of 5-HT induced anorexia disappeared, MAO-A activity had returned to 80% of control values. These results demonstrate that the clorgyline effect is long-lasting and irreversible. Brofaromine (5 mg/kg) and cimoxatone (20 mg/kg) also enhanced the anorectic effect of 5-HT injected 2 h later. The potentiating effects of brofaromine and cimoxatone were not observed when 5-HT was administered 24 h later. These results indicate that brofaromine and cimoxatone are short-acting, reversible inhibitors of MAO-A activity in vivo. Moclobemide (30 mg/kg) failed to enhance the anorectic action of 5-HT injected 2 and 24 h later. The potentiation of 5-HT induced anorexia may be a useful behavioural test for investigating the degree of reversibility, and time course of action of MAOIs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00444703
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  • 3
    Electronic Resource
    Electronic Resource
    Effects ofd-fenfluramine and metergoline on responding for conditioned reward and the response potentiating effect of nucleus accumbensd-amphetamine (1995)
    Springer
    Psychopharmacology 118 (1995), S. 155-163 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned reward ; d-Fenfluramine ; d-Amphetamine ; Metergoline ; Nucleus accumbens ; 5-Hydroxytryptamine dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These studies investigated the effects of the 5-hydroxytryptamine (5-HT) releaser, and re-uptake inhibitor,d-fenfluramine, and the non-selective 5-HT receptor antagonist metergoline, on responding for conditioned reward (CR), and on the potentiation of responding for CR following amphetamine injected into the nucleus accumbens. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase, water was not delivered but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers; responding on the other lever was not reinforced. Overall, rats responded at a higher rate on the lever delivering the CR.d-Amphetamine (1, 3 and 10 µg) injected into the nucleus accumbens dose-dependently enhanced responding on the CR lever. Treatment withd-fenfluramine (0.5 and 1 mg/kg) reduced responding for the CR, and abolished the potentiating effect ofd-amphetamine. Responding on the inactive lever was also reduced by 1 mg/kg but not 0.5 mg/kgd-fenfluramine. The reduction ofd-amphetamine's effect on responding for CR was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Control experiments showed that changes in thirst and motor performance, as well as deficits in learning ability, cannot account for the effects ofd-fenfluramine in this paradigm. In a separate experiment, 1 mg/kg metergoline failed to enhance responding for CR, and to augment the response potentiating effect of a low dose (2 µg) ofd-amphetamine injected into the nucleus accumbens. Thus, elevating brain 5-HT activity appears to reduce the ability of secondary reinforcing stimuli to elicit and maintain behaviour, and antagonizes the effects of enhanced dopamine activity within the nucleus accumbens. However, reduced 5-HT function induced by blockade of 5-HT1/2 receptors does not appear to influence responding for CR, or the response potentiating effect ofd-amphetamine. These results suggest that 5-HT may play an important role in mediating incentive motivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245834
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  • 4
    Electronic Resource
    Electronic Resource
    Further studies to examine the nature of dexfenfluramine-induced suppression of heroin self-administration (1995)
    Springer
    Psychopharmacology 120 (1995), S. 134-141 
    Details
    ISSN: 1432-2072
    Keywords: Dexfenfluramine ; 5-HT receptor subtypes ; Tolerance ; Heroin self-administration ; Rat ; Metergoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present series of experiments sought to investigate further the mechanism by which dexfenfluramine, a selective 5-HT releaser/reuptake inhibitor, reduces heroin self-administration by male Wistar rats. In experiment 1, the effect of combined intravenous heroin and intraperitoneal dexfenfluramine injections on operant responding for food was examined. In experiment 2, the maintenance of dexfenfluramine suppression of heroin self-administration following chronic (7 day) treatment was evaluated. Finally, in experiment 3, the ability of various 5-HT antagonists to block the dexfenfluramine suppression was examined. The results from experiment 1 suggest that sensorimotor deficits/malaise potentially associated with heroin/dexfenfluramine combinations are unlikely to account for the reductions in heroin self-administration. Experiment 2 suggested that the suppressant effect of dexfenfluramine on heroin responding may diminish rapidly following chronic treatment. Finally, central 5-HT1 and/or 5-HT2, but not 5-HT3, receptors may underlie the suppressant effects of dexfenfluramine on heroin self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246185
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  • 5
    Electronic Resource
    Electronic Resource
    Depletion of brain serotonin following intra-raphe injections (1999)
    Springer
    Psychopharmacology 146 (1999), S. 185-193 
    Details
    ISSN: 1432-2072
    Keywords: Key words Serotonin ; Dopamine ; 5 ; 7-Dihydroxytryptamine ; Amphetamine ; Self-administration ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: These experiments investigated the effects of selective serotonin (5-HT) depletion on intravenous self-administration of d-amphetamine. Methods: Depletion of brain 5-HT levels was induced by injecting the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei. Rats were then trained to self-administer d-amphetamine according to various schedule and access conditions via chronically indwelling intravenous catheters. Results: Large reductions of brain 5-HT did not alter responding for a training dose of 120 µg/kg d-amphetamine delivered according to a fixed ratio 1 schedule during 3-h sessions. When the dose of d-amphetamine was altered (0, 3.75, 7.5, 15, 30, 60 µg/kg per infusion) a characteristic inverted U-shaped dose response function was obtained. The 5-HT depleted rats showed increased responding for the lower doses of d-amphetamine, with a large significant increase in responding for the 7.5 µg/kg dose. In these same rats, the suppressive effect of 10 mg/kg fluoxetine on d-amphetamine (60 µg/kg) self-administration was prevented. The 5,7-DHT lesion also did not alter responding for d-amphetamine (120 µg/kg) in longer (8 h) daily access sessions. Responding for d-amphetamine delivered on a progressive ratio schedule, in which response requirements increased for each successive infusion of d-amphetamine, was also determined in 5-HT depleted rats. The number of d-amphetamine infusions was not different from the number of infusions earned by sham-lesioned rats across a range of doses of d-amphetamine (7.5–60 µg/kg). In a final experiment, spontaneous acquisition of self-administration of low doses of d-amphetamine (10 and 30 µg/kg) was measured in 5-HT depleted and control rats. Again, self-administration behaviour in the 5-HT depleted rats did not differ from controls. Conclusions: These results provide no evidence that reducing 5-HT function alters the primary reinforcing effects of self-administered amphetamine. The increase in self-administration of a low dose of amphetamine observed in experiment 1 probably involves some other process such as increased resistance to extinction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051105
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  • 6
    Electronic Resource
    Electronic Resource
    8-OH-DPAT elicits gnawing, and eating of solid but not liquid foods (1987)
    Springer
    Psychopharmacology 92 (1987), S. 192-195 
    Details
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Solid food ; Glucose solution ; Gnawing ; Eating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioural specificity of the eating elicited by the serotonergic agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was investigated. In non-deprived rats 8-OH-DPAT (60–240 μg/kg) increased the consumption of solid food pellets. The consumption of an 18% glucose solution was unaffected by 60 μg/kg 8-OH-DPAT, and markedly reduced by 120 μg/kg 8-OH-DPAT. When rats were pre-fed glucose, to reduce glucose intake under control conditions, 60 μg/kg 8-OH-DPAT significantly decreased subsequent glucose consumption. The failure of 8-OH-DPAT to induce a hyperphagic response to glucose suggests that this compound does not elicit eating by an action upon feeding motivation. Observational analyses showed that 8-OH-DPAT-treated rats exhibited several oro-facial motor responses, including gnawing, which were attenuated by pretreatment with haloperidol. It is likely, therefore, that the increase in solid food intake elicited by 8-OH-DPAT is incidental to drug-induced gnawing. Possible mechanisms of this action are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177914
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  • 7
    Electronic Resource
    Electronic Resource
    Injection of 5-HT into the nucleus accumbens reduces the effects ofd-amphetamine on responding for conditioned reward (1996)
    Springer
    Psychopharmacology 126 (1996), S. 62-69 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; Nucleus accumbens ; d-Amphetamine ; Conditioned reward ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Injection ofd-amphetamine into the nucleus accumbens potentiates responding for stimuli paired with a primary reward. A previous study showed that this potentiating effect ofd-amphetamine on responding for conditioned reward (CR) was attenuated by peripherally injectedd-fenfluramine, a 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. The present experiments further examined the effects of manipulating 5-HT function within the nucleus accumbens on responding for CR, and on the potentiation of CR responding following intra-accumbens injection ofd-amphetamine. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase water was not delivered, but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers. Rats responded at a higher rate on the lever delivering this CR.d-Amphetamine (10 μg) injected into the nucleus accumbens enhanced responding on the CR lever. Co-injections of 5-HT (5 and 10 μg) into the nucleus accumbens abolished the response-potentiating effect ofd-amphetamine but were without effect on the base-line level of responding for CR. This reduction by 5-HT of the response potentiating effect ofd-amphetamine was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Responding for water was not altered by 5-HT and so the effects of 5-HT on responding for CR cannot be due to a change in the motivation to seek the primary reward. Thus, elevating 5-HT activity within the nucleus accumbens antagonises the effects ofd-amphetamine on responding for CR within the nucleus accumbens. These results suggest that 5-HT within the nucleus accumbens may play an important role in mediating incentive motivation by modulating dopaminergic neurotransmission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246412
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  • 8
    Electronic Resource
    Electronic Resource
    Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats (1998)
    Springer
    Psychopharmacology 135 (1998), S. 169-174 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug self-administration ; Alcohol ; Relapse ; Reinstatement ; Stress ; Sucrose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies using a reinstatement procedure have found that acute reexposure to the self-administered drug and exposure to footshock stress reinstate heroin and cocaine seeking after prolonged drug-free periods. Here we tested whether these findings generalize to alcohol-taking behavior. Male rats were initially allowed to consume alcohol in a two-bottle choice procedure (water versus alcohol) for 30 min/day for 36 days. Rats were then trained for 60 min/day in operant chambers to press a lever for the drug (0.13 ml of 12% w/v of an alcohol solution) for up to 55 days. After stable drug-taking on a fixed-ratio-3 schedule of reinforcement was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 4–9 days. Reinstatement of drug seeking was then determined after non-contingent priming injections of alcohol (0.24 and 0.48 g/kg; given IP and orally) or exposure to intermittent footshock stress (5 and 15 min; 0.8 mA). Priming injections of alcohol produced a modest dose-dependent reinstatement of drug seeking, whereas footshock stress potently reinstated extinguished alcohol seeking. In contrast, similar parameters of footshock failed to reinstate extinguished sucrose-taking behavior in rats previously trained to lever press for sucrose pellets. These findings extend previous reports on reinstatement of cocaine and heroin seeking by a footshock stressor and by priming drug injections. It also appears that the reinstatement procedure provides an appropriate methodology to study relapse to alcohol-taking behavior in the drug-free state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050498
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  • 9
    Electronic Resource
    Electronic Resource
    Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction (1999)
    Springer
    Psychopharmacology 141 (1999), S. 421-427 
    Details
    ISSN: 1432-2072
    Keywords: Key words SSRI ; Cytochrome P450 ; Serotonin ; Microdialysis ; Norfluoxetine ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5–1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050852
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  • 10
    Electronic Resource
    Electronic Resource
    The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin (1999)
    Springer
    Psychopharmacology 143 (1999), S. 426-432 
    Details
    ISSN: 1432-2072
    Keywords: Key words SSRI ; Dorsal raphé ; Median raphé ; 5-Hydroxytryptamine ; 5 ; 7-Dihydroxytryptamine ; Cytochrome P450 ; Wistar rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sertraline dose-dependently increased the locomotor stimulating effect of amphetamine. At the highest dose, 20 mg/kg sertraline had a biphasic effect on amphetamine-induced hyperactivity, producing an initial reduction in amphetamine-induced hyperactivity that was later followed by an augmentation of amphetamine-induced hyperactivity in the last hour of the 3-h test. Sertraline, at doses of 5 and 10 mg/kg, produced an augmentation of amphetamine-induced hyperactivity over the last 2 h of the 3-h test session. Further, there was an increase in the concentration of amphetamine in the brain in rats pretreated with 5 mg/kg sertraline. Both sertraline (5 mg/kg) and fluoxetine (5 mg/kg) produced an augmentation of amphetamine-induced hyperactivity that was unaltered by a serotonergic lesion of the median and dorsal raphé nuclei that resulted in a greater than 90% depletion of serotonin in hippocampus, striatum, and nucleus accumbens. Further, both sertraline and fluoxetine inhibited spontaneous locomotor activity and this effect was also unaltered by the depletion of serotonin. Thus, serotonergic neurotransmission is not essential for the effects of sertraline and fluoxetine on spontaneous and amphetamine-induced locomotion. It is probable that sertraline and fluoxetine augment the locomotor stimulatory effect of amphetamine by decreasing the metabolism of amphetamine, perhaps via actions on cytochrome P450 isozymes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050968
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