Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.

• Klíčová slova
• depression, olfactory bulbectomy, reward, self-administration, sex, strain,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Addiction is a chronic disease with limited pharmacological options for intervention. Focusing on reducing glutamate levels in the brain seems to be a promising strategy in addiction treatment research. Our research aimed to evaluate the effects of CNQX, an antagonist that targets AMPA and kainate glutamatergic receptors while also exhibiting affinity for the NMDA receptor, especially by modulating its glycine site. We conducted this assessment on the self-administration of nicotine and methamphetamine via intravenous (IV) administration in rats. METHODS: An operant IV self-administration model was used in male Wistar rats. When animals maintained a stable intake of nicotine or methamphetamine, we administered a single injection of CNQX (in the dose of 3 or 6 mg/kg IV) to evaluate its effect on drug intake. Subsequently, the rats were forced to abstain by staying in their home cages for 2 weeks. The period of abstinence was followed by a context-induced relapse-like session before which animals were pretreated with the injection of CNQX (3 or 6 mg/kg IV) to evaluate its effect on drug seeking. RESULTS: CNQX significantly reduced nicotine intake during the maintenance phase, but no effect was revealed on nicotine seeking after forced abstinence. CNQX did not affect methamphetamine taking or seeking. CONCLUSION: The effect of reducing nicotine taking but not seeking could be explained by different involvement of glutamatergic receptors in various stages of nicotine dependence.

• Klíčová slova
• AMPA/kainate receptor, CNQX, methamphetamine, nicotine, relapse, self-administration,
• Publikační typ
• časopisecké články MeSH

Substance abuse and depression are common psychiatric disorders with a high rate of comorbidity. Both conditions affect differently men and women and preclinical research has showed many sex differences in drug addiction and depression. The most common approach for modeling depression-addiction comorbidity is the combination of the intravenous drug self-administration and the olfactory bulbectomy (OBX) models in rats. Such a combination has revealed enhanced drug-taking and drug-seeking behaviors in OBX rats, but no study has investigated so far potential sex differences in operant responding and motivation for natural reinforcers in OBX rats. This study investigated for the first time operant self-administration of palatable food pellets in male and female OBX rats under different feeding status, i.e., ad libitum vs. restricted food, and schedules of reinforcement, i.e., a continuous ratio schedule fixed ratio 1 (FR1) vs. a complex (FR5(x)) second order schedule of reinforcement. In the FR1 experiment, OBX rats of both sexes exhibited lower operant responding and intake of palatable food pellets than sham-operated controls, with food restriction leading to increased operant responding in both OBX and SHAM groups. Female rats showed higher responding than males but this effect was abolished by the OBX lesion. Similarly, in the (FR5(x)) second order schedule of reinforcement both male and female OBX rats showed lower responding and food intake, with SHAM and OBX females showing higher operant responding than corresponding male groups. Overall, our findings showed that: (i) responding for food was lower in OBX than in SHAM rats under both FR1 and (FR5(x)) schedules of reinforcement; (ii) sex and food restriction affect operant responding for palatable food; and (iii) the suppressing effect of OBX lesion on food intake was consistently present in both sexes and represents the most robust factor in the analysis. This may represent anhedonia which is associated with depressive-like phenotype and palatable food self-administration may serve as a robust behavioral index of anhedonia in the OBX model.

• Klíčová slova
• depression, food intake, olfactory bulbectomy, reward, self-administration, sex difference,
• Publikační typ
• časopisecké články MeSH

The opioid-induced rise of extracellular dopamine, endocannabinoid anandamide and γ-aminobutyric acid (GABA) concentrations triggered by opioids in the nucleus accumbens shell (NACSh) most likely participate in opioid reward. We have previously demonstrated that systemic administration of ghrelin antagonist (JMV2959) significantly decreased morphine-induced dopamine and anandamide (N-arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist. The aim of this study was to test whether JMV2959, a growth hormone secretagogue receptor (GHS-R1A) antagonist, can influence the fentanyl-induced effects on anandamide, 2-arachidonoylglycerol (2-AG) and GABA in the NACSh and specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and nucleus accumbens (NAC). Using in vivo microdialysis in rats, we have found that pre-treatment with JMV2959 reversed dose dependently fentanyl-induced anandamide increases in the NACSh, resulting in a significant AEA decrease and intensified fentanyl-induced decreases in accumbens 2-AG levels, with both JMV2959 effects more expressed when administered into the NACSh in comparison to the VTA. JMV2959 pre-treatment significantly decreased the fentanyl-evoked accumbens GABA efflux and reduced concurrently monitored fentanyl-induced behavioural stimulation. Our current data encourage further investigation to assess if substances affecting GABA or endocannabinoid concentrations and action, such as GHS-R1A antagonists, can be used to prevent opioid-seeking behaviour.

• Klíčová slova
• 2-arachidonoylglycerol, GABA, anandamide, endocannabinoids, fentanyl, ghrelin, microdialysis, neural reward system, nucleus accumbens shell, ventral tegmental area,
• MeSH
• chování zvířat MeSH
• endokanabinoidy metabolismus   MeSH
• extracelulární prostor metabolismus   MeSH
• fentanyl farmakologie   MeSH
• GABA metabolismus   MeSH
• ghrelin farmakologie   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• krysa rodu Rattus MeSH
• nucleus accumbens účinky léků   metabolismus   MeSH
• receptory ghrelinu metabolismus   MeSH
• tegmentum mesencephali - area ventralis účinky léků   metabolismus   MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokanabinoidy MeSH
• fentanyl MeSH
• GABA MeSH
• ghrelin MeSH
• glycin MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• receptory ghrelinu MeSH
• triazoly MeSH