Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

Homberg, Judith R.; Boer, Sietse F. de; Raasø, Halfdan S; Olivier, Jocelien; Verheul, Mark; Ronken, Eric; Cools, Alexander R.; Ellenbroek, Bart A.; Schoffelmeer, Anton N. M.; Vanderschuren, Louk J. M. J.; Vries, Taco J. De; Cuppen, Edwin

doi:10.1007/s00213-008-1212-x

Cited by 98 publications

(94 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Roberts et al (1994) reported increased breakpoints for cocaine in a progressive-ratio schedule of reinforcement following global depletion of 5-HT in the brain (see also : Loh and Roberts 1990). This view is also supported by a recent study in serotonin transporter knockout rats, which showed enhanced cocaine-induced hyperlocomotion, CPP, as well as enhanced cocaine self-administration (Homberg et al 2008). These findings implicate an increase of the incentive value of cocaine and, therefore, would suggest that 5-HT has an inhibitory role in cocaine-mediated reinforcement.…”

Section: Discussionmentioning

confidence: 59%

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

et al. 2008

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 59%

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

et al. 2008

View full text Add to dashboard Cite

show abstract

“…However, depending on the behavioral effect of cocaine, enhanced NE and 5-HT release (upon blockade of NET and SERT) may also play a role (Drouin et al, 2002;Homberg et al, 2008;Hall et al, 2009 Since an inhibitory effect of insulin on electrically evoked monoamine release in brain slices was associated with potentiation of the release-enhancing effect of monoamine transporter blockers, our study reveals that insulin presynaptically enhances the function of monoamine transporters in frontal cortical and striatal rat brain regions.…”

mentioning

confidence: 75%

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

et al. 2011

View full text Add to dashboard Cite

Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [ 3 H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [ 3 H]norepinephrine in nucleus accumbens slices, but not on that of [ 3 H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocainesensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

show abstract

“…In agreement with the large literature implicating 5-HT in the pathophysiology and treatment of mood and anxiety disorders, SERT-deficient (−/− and +/-) mice showed an anxiogenic phenotype, which was ameliorated by a 5-HT1A antagonist (215, 220, 228, 229). Cognitive assays showed SERT−/− rodents may perform better in emotionally guided/motivated learning, but worse in “neutral” tasks - perhaps related to the anxiety-like phenotype (230, 231). Consistently, a SERT-overexpressing mouse line showed a phenotype opposite to the SERT−/− in many respects: reduced extracellular and total 5-HT levels, and decreased anxiety-like behaviors (232, 233).…”

Section: Animal Geneticsmentioning

confidence: 99%

Monoamine Transporters

Lin¹,

Canales²,

Björgvinsson³

et al. 2011

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

Transporters of dopamine, serotonin and norepinephrine have been empirically used as medication targets for several mental illnesses for the last decades. These protein-targeted medications are effective only for subpopulations of patients with transporter-related brain disorders. Since the cDNA clonings in early 1990’s, molecular studies of these transporters have revealed a wealth of information about the transporters’ structure activity relationship (SAR), neuropharmacology, cell biology, biochemistry, pharmacogenetics and the diseases related to the human genes encoding these transporters among related regulators. Such new information creates a unique opportunity to develop transporter-specific medications based on SAR, mRNA, DNA and perhaps transporter trafficking regulation, for a list of highly relevant diseases including substance abuse, depression, schizophrenia and Parkinson’s disease.

show abstract

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

Cited by 98 publications

References 58 publications

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

Monoamine Transporters

Contact Info

Product

Resources

About