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  • 1
    ISSN: 1432-2072
    Keywords: Key words Antidepressant drug ; Dopamine receptor ; Nucleus accumbens ; In situ hybridisation ; Receptor autoradiography ; Microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D2 mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D1 mRNA in any of the regions examined. Measurement of D2-like binding by receptor autoradiography, using the ligand [3H]YM-09151-2, revealed that both fluoxetine and desipramine increased D2-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D2-like binding in the nucleus accumbens but decreased binding in the striatum. In microdialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of postsynaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).
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  • 2
    ISSN: 1432-2072
    Keywords: Gepirone ; Buspirone ; Ipsapirone ; Glucose utilization ; Hippocampus ; Lateral habenular nucleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxyglucose autoradiography. All three 5-HT1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20–25% and increased glucose utilization by 38–65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbichabenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Dopamine ; Electroconvulsive shock ; Antidepressants ; Nucleus accumbens ; In situ hybridisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effects of acute and repeated administration of electroconvulsive shock (ECS) on levels of D1 and D2 receptor mRNAs in the nucleus accumbens and striatum (caudate-putamen) of the rat. Quantitative in situ hybridisation with35S-labelled oligonucleotide probes specific for D1 and D2 receptor mRNAs was utilised. Compared to controls, rats receiving a single ECS showed higher levels of both D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after treatment. Similarly, rats receiving ECS repeatedly (five ECS in 10 days) also exhibited higher levels of D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after the last treatment. The effects of single and repeated ECS treatment on dopamine receptor mRNA levels were localised to the caudal region of the nucleus accumbens. No statistically significant changes in mRNA levels were detected in the striatum of rats treated with either acute or repeated ECS. We discuss the possibility that increased expression of D1 and D2 receptors in the nucleus accumbens may be involved in the dopamine-enhancing properties of ECS detected in behavioural studies.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 339-346 
    ISSN: 1432-1912
    Keywords: 5-HT1A receptor ; Microdialysis ; 8-OHDPAT ; Buspirone ; Ipsapirone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Electrophysiological measurements of 5-HT neuronal activity report that repeated administration of 5-HT1A receptor agonists leads to desensitization of the 5-HT1A autoreceptor but this has not yet been detected in measurements of brain 5-HT synthesis or metabolism. Here we have determined the effect of repeated administration of 5-HT1A receptor agonists on brain 5-HT release using microdialysis. 2. Acute administration of the 5-HT1A receptor agonists buspirone (0.1–5 mg/kg s.c.) and ipsapirone (0.03–3 mg/kg s.c.) caused a dose-dependent decrease in 5-HT output in ventral hippocampus of the chloral hydrate anaesthetized rat. 3. The 5-HT response to buspirone (0.1 and 0.5 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was significantly inhibited by pre-treatment with the 5-HT1/β-adrenoceptor antagonist pindolol (8–16 mg/kg s.c.). The 5-HT response to buspirone (0.1 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was not blocked by pretreatment with a combination of the β1 and β2-adrenoceptor antagonists metoprolol and ICI 118,551 (4 mg/kg s.c.). 4. The effect of an acute challenge of buspirone (0.5 mg/kg s.c.) on 5-HT output in ventral hippocampus was not attenuated in rats treated twice daily for 14 days with 0.5 or 5 mg/kg s.c. buspirone compared to saline-injected controls. Similarly, the decrease in 5-HT induced by an acute challenge of ipsapirone (0.5 mg/kg s.c.) was not attenuated in rats treated twice daily for 14 days with 5 mg/kg s.c. ipsapirone. 5. In further experiments it was shown that the decrease in 5-HT induced in both ventral hippocampus and striatum by an acute challenge of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.025 mg/kg s.c.), was not attenuated in rats treated twice daily for 14 days with 1 mg/kg s.c. 8-OH-DPAT. 6. Basal levels of 5-HT in hippocampal and striatal microdialysates of animals treated repeatedly with the 5-HT1A receptor agonists were not consistently altered relative to treatment controls. 7. In agreement with earlier studies measuring regional brain 5-HT synthesis and metabolism, the present microdialysis measurements of 5-HT release indicate that the inhibitory effect of 5-HT1A receptor agonists on presynaptic 5-HT function is maintained in rats treated repeatedly with the same drugs.
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