Repeated administration of amphetamine-like psychostimulants produce a progressive and long-lasting hypersensitivity to their behavioural effects known as behavioural sensitization. Previous studies have shown that administration of the purinergic P2 receptor agonist 2-methylthio ATP into the nucleus accumbens of rats raises the extracellular level of dopamine accompanied with enhanced locomotion in a similar manner. Furthermore, the quantitative EEG after application of 2-methylthio ATP or amphetamine was characterized by an elevation of the alpha1-power. However, purinergic P2 receptor antagonists decreased the basal level of dopamine in the NAc and in addition prevented the effects of 2-methylthio ATP. The purpose of the present study was to investigate, whether endogenous ATP acting via purinergic P2 receptors is involved in the process of amphetamine-induced sensitization. Rats were treated systemically for five successive days with d-amphetamine (1.5 mg/kg) and tested in an open field with respect to their locomotor response. The enhanced locomotor activity after the first injection of amphetamine was diminished by the previous intracerebroventricular application of the purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS; 0.6 nmol) (P<0.05). The challenge with a lower dose of amphetamine (0.75 mg/kg) produced an increased locomotion in comparison to the response after the first amphetamine application indicating the expression of a behavioural sensitization. Pretreatment with PPADS prior to each amphetamine administration prevented the increase of locomotor activity after the challenge with amphetamine (P<0.05). In summary, the present study demonstrates that PPADS blocks both the acute locomotor effects of amphetamine and the development of behavioural sensitization to the psychostimulant. We suggest that the activation of purinergic P2 receptors by endogenous ATP is necessary for the expression of these effects.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0306-4522(00)00555-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pyrimidinergic P2Y1-Like Nucleotide Receptors Are Functional in Rat Conjunctival Goblet Cells.
Invest Ophthalmol Vis Sci
January 2025
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
Purpose: To investigate the presence of uridine-5'-triphosphate (UTP)-activated P2Y1-like nucleotide receptors (P2Y2R, P2Y4R, and P2Y6R) in conjunctival goblet cells (CGCs) and determine if they increase intracellular Ca2+ concentration ([Ca2+]i) and induce mucin secretion.
Methods: Adult, male rat conjunctiva was used for culture of CGCs. To investigate the expression of P2YRs, mRNA was extracted from CGCs and used for reverse transcription PCR (RT-PCR) with commercially obtained primers specific to P2Y2R, P2Y4R, and P2Y6R.
Adenosine diphosphate stimulates VEGF-independent choroidal endothelial cell proliferation: A potential escape from anti-VEGF therapy.
Proc Natl Acad Sci U S A
January 2025
Department of Pathology, University of California San Diego, La Jolla, CA 92093.
We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts.
View Article and Find Full Text PDFKnowledgebase-Driven Exploration and Experimental Verification of Simvastatin's Inhibitory Impact on P2X7/NLRP3 Inflammasome Pathway.
Chem Biol Drug Des
January 2025
College of Pharmacology Sciences, Zhejiang University of Technology, Hangzhou, People's Republic of China.
Depression is a mental health disorder and is the fourth most prevalent disease. Previous studies have suggested that statins are involved in the reduction of neuroinflammation. However, the potential mechanism for this relationship is unclear.
View Article and Find Full Text PDFExtracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells.
Purinergic Signal
January 2025
Department of Biology, Faculty of Science, University of British Columbia Okanagan Campus, Kelowna, BC, V1V 1V7, Canada.
The two main glial cell types of the central nervous system (CNS), astrocytes and microglia, are responsible for neuroimmune homeostasis. Recent evidence indicates astrocytes can participate in removal of pathological structures by becoming phagocytic under conditions of neurodegenerative disease when microglia, the professional phagocytes, are impaired. We hypothesized that adenosine triphosphate (ATP), which acts as damage-associated molecular pattern (DAMP), when released at high concentrations into extracellular space, upregulates phagocytic activity of human astrocytes.
View Article and Find Full Text PDFInactivated SARS-CoV-2 induces acute skeletal muscle damage in human K18-hACE2 transgenic mice.
Life Sci
January 2025
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:
The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in over 7 million global fatalities and billions of individuals diagnosed with COVID-19. Acute and chronic muscle impairment associated with SARS-CoV-2 infection affected a substantial number of patients, leading to the development of symptoms such as fatigue, muscle pain, and exercise intolerance. Our study introduces an animal model to improve understanding of the pathogenicity caused by SARS-CoV-2 in human skeletal muscle.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!