Long-term partial 5-HT depletion: interference of anxiety and impulsivity?

Harro, Jaanus

doi:10.1007/s00213-002-1265-1

Cited by 25 publications

(14 citation statements)

References 17 publications

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“…Alternatively, there is the possibility that non-serotonergic mechanisms are also involved in the acute effects of MDMA upon aggression, including dopamine, glutamate or GABA (Sexton et al, 1999). It is also possible that anxiety, reactivity and impulsivity confound the overt behavioural expression of MDMA-induced effects, as has previously been described after partial 5-HT depletion (Green et al, 2003 ;Harro, 2002). There was, however, a difference in drug-induced motor activation.…”

Section: Acute Effects Of Mdma On Aggression and Lcmr Glumentioning

confidence: 86%

Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

Kirilly

Benko

Ferrington

et al. 2005

Int. J. Neuropsychopharm.

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MDMA causes selective depletion of serotonergic terminals in experimental animals and the consequent decrease in synaptic 5-HT may, inter alia, increase impulsivity. To study the effects of MDMA upon brain function, the behaviour of male Dark Agouti rats exposed to MDMA (15 mg/kg i.p.), two 5-HT1B agonists (CGS-12066A and CP-94,253, both 5 mg/kg i.p.) or saline were investigated in the resident-intruder test. Studies were performed in drug-naive rats and also in rats exposed to MDMA (15 mg/kg i.p.) 21 d earlier. In parallel experiments the functional neuroanatomy of MDMA effects were assessed using 2-deoxyglucose imaging of local cerebral metabolic rate of glucose utilization (LCMRGlu) and neurotoxicity was assessed by measuring [3H]paroxetine binding. There was no significant difference in aggressive behaviour (biting, boxing, wrestling and their latencies) between drug-naive rats and rats previously exposed to MDMA 21 d earlier, despite reduced social behaviour, decreased LCMRGlu in several brain areas involved in aggression, and reductions in paroxetine binding by 30-60% in the forebrain. CGS-12066A, CP-94,253 and acute MDMA produced marked decreases in aggressive behaviours, especially in biting, boxing and kicking found in drug-naive rats. In animals previously exposed to the drug, acute anti-aggressive effects of MDMA were, in general, preserved as were MDMA-induced increases in LCMRGlu. Our studies provide evidence that in the resident-intruder test, where social isolation is a requirement, aggressive behaviour and acute anti-aggressive effects of MDMA and 5-HT1B receptor agonists remain intact 3 wk after a single dose of the drug despite significant damage to the serotonergic system.

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Section: Acute Effects Of Mdma On Aggression and Lcmr Glumentioning

confidence: 86%

Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

Kirilly

Benko

Ferrington

et al. 2005

Int. J. Neuropsychopharm.

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“…One explanation for this discrepancy is that the ICSS and forced swim test procedures may reflect two unique aspects of depression-like behavior – respectively, anhedonia and behavioral despair – that may not always correlate. Interestingly, chronic variable stress also decreased immobility in the forced swim test, an effect that was attributed to increased impulsivity (52, 53). Moreover, impulsivity correlates strongly with anhedonia and avolition in depressive disorders (54).…”

Section: Discussionmentioning

confidence: 97%

Enduring Deficits in Brain Reward Function after Chronic Social Defeat in Rats: Susceptibility, Resilience, and Antidepressant Response

Der-Avakian

Mazei-Robison

Kesby

et al. 2014

Biological Psychiatry

138

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Background Anhedonia, or diminished interest or pleasure in rewarding activities, characterizes depression and reflects deficits in brain reward circuitries. Social stress induces anhedonia and increases depression risk, although the effect of social stress on brain reward function remains incompletely understood. Methods We assessed: 1) brain reward function in rats (using the intracranial self-stimulation procedure) and protein levels of brain-derived neurotrophic factor (BDNF) and related signaling molecules in response to chronic social defeat; 2) brain reward function during social defeat and chronic treatment with the antidepressants fluoxetine (5 mg/kg/day) or desipramine (10 mg/kg/day); and 3) forced swim test behavior after social defeat and fluoxetine treatment. Results Social defeat profoundly and persistently decreased brain reward function, reflecting an enduring anhedonic response, in susceptible rats, while resilient rats showed no long-term brain reward deficits. In the ventral tegmental area (VTA), social defeat, regardless of susceptibility or resilience, decreased and increased BDNF and phosphorylated AKT, respectively, whereas only susceptibility was associated with increased phosphorylated mammalian target of rapamycin (mTOR). Fluoxetine and desipramine reversed lower, but not higher, stress-induced brain reward deficits in susceptible rats. Fluoxetine decreased immobility in the forced swim test, as did social defeat. Conclusions These results suggest that the differential persistent anhedonic response to psychosocial stress may be mediated by VTA signaling molecules independent of BDNF, and indicate that greater stress-induced anhedonia is associated with antidepressant treatment resistance. Consideration of these behavioral and neurobiological factors associated with resistance to stress and antidepressant action may promote the discovery of novel targets to treat stress-related mood disorders.

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“…This proposal has been taken further by Harro (2002), who presented further evidence that impulsivity following 5-HT depletion might present as an anxiolytic effect in the plus maze. It has also recently been demonstrated that lowering cerebral serotonin levels by rapid depletion of tryptophan in normal human individuals increases impulsiveness (Walderhaug et al, 2002), which provides some support for the Mechan et al (2002b) interpretation of their data.…”

Section: Long-term Functionalmentioning

confidence: 91%

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

et al. 2003

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Long-term partial 5-HT depletion: interference of anxiety and impulsivity?

Cited by 25 publications

References 17 publications

Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

Enduring Deficits in Brain Reward Function after Chronic Social Defeat in Rats: Susceptibility, Resilience, and Antidepressant Response

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

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