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  • 1
    Electronic Resource
    Electronic Resource
    Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine (1994)
    Springer
    Psychopharmacology 115 (1994), S. 441-446 
    Details
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Imipramine ; Animal model of depression ; Dopamine ; D1-receptors ; D2-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245566
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  • 2
    Electronic Resource
    Electronic Resource
    Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline (1992)
    Springer
    Psychopharmacology 109 (1992), S. 433-438 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Sucrose drinking ; Place preference conditioning ; Reward ; Fluoxetine ; Maprotiline ; Chlordiazepoxide ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions. In the present study this effect was reversed by chronic (9 weeks) treatment with the atypical antidepressants, fluoxetine and maprotiline (5 mg/kg/day); the non-antidepressant chlordiazepoxide was ineffective. Stressed animals were also subsensitive to food reward in the place conditioning procedure; however, fluoxetine and maprotiline treated animals showed normal place preference conditioning. Acute pretreatment with raclopride (100 µg/kg) selectively reversed the recovery of sucrose drinking in antidepressant-treated stressed animals. These results extend previous reports of the efficacy of tricyclic antidepressants in this paradigm, and support the hypothesis of a dopaminergic mechanism of antidepressant action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247719
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of imipramine on serotonergic and beta-adrenergic receptor binding in a realistic animal model of depression (1994)
    Springer
    Psychopharmacology 114 (1994), S. 309-314 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Imipramine ; Animal model of depression ; Receptor bind ; Beta-receptors ; 5HT1A receptors ; 5HT2 receptors ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure to mild unpredictable stress (CMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions. In the present study, in addition to confirming these behavioural observations, the binding properties of cortical beta-adrenergic and 5HT2 receptors, and hippocampal 5HT1A receptors were studied (using the ligands [3H]-dihydroalprenolol, [3H]-ketanserin and [3H]-8-OH-DPAT, respectively), following 7 weeks of CMS and 4 weeks of imipramine treatment (10mg/kg per day). CMS increased Bmax for all three receptor systems. Impramine decreased Bmax, reversing the effect of CMS, for beta-adrenergic and 5HT2 receptor binding, but increased Bmax for 5HT1A receptor binding. KDs were unaffected by either treatment. The beta-receptor and 5HT2 receptor binding data are consistent with accounts of antidepressant action derived from studies in normal animals, but the 5HT1A receptor binding data are more difficult to reconcile. In no case was there a good correlation between receptor binding and behavioural data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244853
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  • 4
    Electronic Resource
    Electronic Resource
    8-OH-DPAT-induced place preference and place aversion: effects of PCPA and dopamine antagonists (1991)
    Springer
    Psychopharmacology 103 (1991), S. 99-102 
    Details
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT-PCPA ; Dopamine antagonists ; Conditioned place preference ; Conditioned place aversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of 8-OH-DPAT (62.5–250 µg/kg) were reinforcing in the place preference conditioning procedure, while a higher dose (1 mg/kg) supported a conditioned place aversion. The 5-HT synthesis inhibitor PCPA, and the DA antagonists pimozide and sulpiride, had no effect when administered alone, but abolished the 8-OH-DPAT-induced place preference. However, neither PCPA nor pimozide altered the 8-OH-DPAT-induced place aversion. The results are consistent with other evidence showing that 8-OH-DPAT acts through different mechanisms at low and high doses, and support the hypothesis that low doses of 8-OH-DPAT act through 5-HT neurons to disinhibit dopaminergic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244082
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  • 5
    Electronic Resource
    Electronic Resource
    An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress (1991)
    Springer
    Psychopharmacology 104 (1991), S. 255-259 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Place preference conditioning ; Reward ; Amphetamine ; Anhedonia ; Melancholia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure to very mild unpredictable stress has previously been found to depress the consumption of, and preference for, highly palatable sweet solutions. The present study used the place conditioning procedure to investigate whether these effects result from a decreased sensitivity to reward. Rats were subjected to chronic mild unpredictable stress for a total of 4 weeks. During weeks 3 and 4, they received four training trials, in which rewards were presented in a distinctive environment, and four further non-rewarded trials in a different environment. The rewards used in different experiments were food pellets, dilute (0.7%) and concentrated (34%) sucrose solutions, anddl-amphetamine sulphate (0.5 and 1.0 mg/kg). In all experiments, non-stressed animals showed an increase in preference for the environment associated with reward; in stressed animals, these effects were abolished or greatly attenuated. Chronic unpredictable mild stress, which may be comparable in intensity to the difficulties people encounter in their daily lives, appears to cause a generalized decrease in sensitivity to rewards.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244188
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  • 6
    Electronic Resource
    Electronic Resource
    Pimozide does not impair sweetness discrimination (1990)
    Springer
    Psychopharmacology 102 (1990), S. 278-282 
    Details
    ISSN: 1432-2072
    Keywords: Sucrose ; Preference ; Discrimination ; 2-Bottle test ; T-maze ; Pimozide ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an initial experiment pimozide decreased preference for a weak sucrose solution but increased preference for a strong solution on the descending limb of the concentration-intake function. As these effects resemble those of dilution, we therefore investigated whether pimozide decreases the perceived intensity of sweet stimuli. Rats were trained to perform a conditional discrimination in a T-maze. A correct response was rewarded by access to a 10% sucrose solution; an incorrect response was punished by confinement in the non-rewarded arm. In the first part of this experiment the discriminative stimulus, located at the choice point of the T-maze, was either water or sucrose, initially a 10% solution, but reduced gradually to 0.0003%. In the second part of the experiment, the discriminative stimulus was either 1% sucrose or a weaker solution, which was initially 0.0001% then raised gradually to 0.5%. Performance fell below 75% accuracy at 0 versus 0.0012% and at 1% versus 0.1%. Pimozide (0.5 mg/kg) administered at these (and other) levels of difficulty decreased running speed but had no effect on discrimination accuracy. As pimozide did not affect either the threshold for sweetness perception or the discrimination of a just noticeable difference, the decreased responsiveness of neuroleptic-treated rats to sweet rewards cannot be explained by a change in the perception of sweetness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245934
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  • 7
    Electronic Resource
    Electronic Resource
    Behavioural sensitization to a dopamine agonist is associated with reversal of stress-induced anhedonia (1993)
    Springer
    Psychopharmacology 110 (1993), S. 159-164 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Sucrose consumption ; Place preference conditioning ; Reward ; Quinpirole ; Behavioural sensitization ; Dopamine ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure to very mild unpredictable stress (CMS) has previously been found to reduce the consumption of palatable sweet solutions and to impair place preference conditioning; evidence has been presented that these effects may reflect a dysfunction of the mesolimbic dopamine system. In the present study, rats were subjected to CMS for a total of 9 weeks. CMS reduced the consumption of a 1% sucrose solution. During weeks 6 and 7, animals received quinpirole (0–400 µg/kg) twice weekly. Both CMS-treated animals and controls showed sensitization to the locomotor stimulant effects of quinpirole. Subsequently, a sustained recovery of sucrose drinking was observed in quinpirole-treated stressed animals. During week 8, all animals received a single pair of place preference conditioning trials, in which quinpirole (200 µg/kg) was administered in a distinctive environment, and vehicle in a different environment. Non-stressed animals showed an increase in preference for the environment associated with quinpirole, as did stressed animals that had been sensitized to quinpirole; this effect was absent in untreated stressed animals. Finally, in week 9, acute administration of raclopride (150 µg/kg) was found to reverse the recovery of sucrose drinking in quinpirole-treated stressed animals, suggesting that these effects are mediated by an increase in dopamine function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246966
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  • 8
    Electronic Resource
    Electronic Resource
    Subsensitivity to rewarding and locomotor stimulant effects of a dopamine agonist following chronic mild stress (1993)
    Springer
    Psychopharmacology 110 (1993), S. 152-158 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Place preference conditioning ; Reward-Locomotor activity ; Amphetamine ; Quinpirole ; Dopamine ; D2 receptor ; Nucleus accumbens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure to very mild unpredictable stress has previously been found to reduce or abolish the acquisition of place preference conditioning. In the present study, chronic mild stress was found to abolish the acquisition of preferences for a distinctive environment paired with systemic administration of amphetamine (0.5 mg/kg) or quinpirole (100–400 µg/kg) or with quinpirole (0.75 µg) administered bilaterally within the nucleus accumbens. The locomotor stimulant effects of quinpirole (100–400 µg/kg) were also attenuated in stressed animals. The results suggest that decreased sensitivity to reward following chronic mild stress results from a decreased sensitivity of dopamine D2 receptors within the nucleus accumbens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246965
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