11 research outputs found
Acute Cocaine Differentially Induces PKA Phosphorylation Substrates in Male and Female Rats
Background: Sex differences in intracellular dopamine pathways may contribute to the known sex differences in psychomotor responses to cocaine and differential development of dependence. This study aimed to determine whether there are sex differences in the activation of the extracellular signal-regulated kinases (ERK1/2, or p44/p42 MAPK) and PKA phosphorylation-dependent substrates in the nucleus accumbens (NAcc) of male and female rats at baseline or after acute cocaine administration.
Methods: 60-day-old male and female Fischer rats were injected with saline or cocaine (30 mg/kg) and sacrificed 5, 15, 30, 45 or 90 minutes later. Total locomotor activity, Stereotypic, rearing, and ambulatory behaviors was measured for 90 minutes using a two-frame automated Photobeam Activity
Results: Similar to our previous findings, total locomotor activities were higher in female rats after this single cocaine administration. Females had higher levels of phosphorylated PKA substrates after cocaine administration, and this change lasted longer and had a greater magnitude than in cocaine treated male rats. Furthermore, although cocaine administration increased the phosphorylation of ERK proteins, there were no sex differences in p-ERK protein levels either at baseline or after acute cocaine administration.
Conclusion: Taken together, these findings suggest that sex differences in basal and cocaine-induced alterations in PKA signaling activity in the NAcc may contribute to sex differences in psychomotor responses to cocaine. However, not all the components of the DA-intracellular signaling pathway maybe heightened in female rats as ERK phosphorylation patterns did not differ between the sexes
A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain
To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86–88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury
Broken Heart Syndrome: A Case Report
Stress-induced cardiomyopathy or Takotsubo cardiomyopathy is a recently increasing diagnosed disease manifested by transient apical or mid left ventricular dilation and dysfunction. This sign is similar to acute myocardial infarction but without significant coronary artery stenosis. There are important and essential differences between Takotsubo cardiomyopathy and acute myocardial infarction in terms of management, necessitating a good understanding of the pathophysiology, diagnosis, and treatment of the former.
We report a case of Takotsubo cardiomyopathy which presented with dizziness and near syncope after an intense emotional stress. Electrocardiogram showed ST-T changes in V1-V3 and echocardiography revealed severe left ventricular systolic dysfunction with marked regional wall motion abnormalities. Coronary angiography demonstrated minimal coronary artery disease.
The patient was treated with beta -blockers, angiotensin-converting enzyme inhibitors, Aspirin, Clopidogrel, and diuretics. At the follow-up visit, all the symptoms had disappeared and control echocardiography showed significant improvement in the left ventricular systolic function with a normal ejection fraction and normal wall motion