Glycogen synthase kinase 3 (GSK-3) is a constitutively active serine-threonine kinase that regulates numerous signaling pathways and has been implicated in neurodegenerative and neuropsychiatric diseases including Alzheimer's, Parkinson's, schizophrenia, and bipolar disorder. Evidence indicates that alcohol exposure increases GSK-3β (ser9) phosphorylation (pGSK-3β); however, few studies have investigated whether GSK-3 regulates the positive reinforcing effects of alcohol, which drive repetitive drug use. This study aimed to address the potential role of GSK-3 in alcohol self-administration by investigating whether direct pharmacological inhibition of GSK-3 alters the positive reinforcing effect of alcohol in mice. Male C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule of sweetened alcohol or sucrose-only reinforcement in operant conditioning chambers. The GSK-3 inhibitor CHIR 99021 trihydrochloride (0-10 mg/kg, ip) was injected 45-min prior to self-administration sessions in a counterbalanced design. After completion of the self-administration dose-effect curve, potential locomotor effects of the GSK-3 inhibitor were assessed. To determine molecular efficacy, CHIR 99021 (10 mg/kg, ip) was evaluated on pGSK-3β, GSK-3β PICK1, and AMPA receptor GluA2 subunit protein expression in amygdala, nucleus accumbens (NAcb), and frontal cortex in the absence of alcohol. CHIR 99021 (10 mg/kg) dose-dependently increased alcohol reinforced responding with no effect on sucrose self-administration or locomotor activity. CHIR 99021 (10 mg/kg) significantly decreased pGSK-3β expression in all brain regions tested, reduced PICK1 and increased GluA2 total expression only in the NAcb. We conclude that GSK-3 inhibition increased the reinforcing effects of alcohol in mice. This was associated with reduced pGSK-3β and PICK1, and increased GluA2 protein expression. Given prior results showing that AMPA receptor activity regulates alcohol selfadministration, we propose that signaling through the GSK-3 / PICK1 / GluA2 molecular pathway drives the positive reinforcing effects of the drug, which are required for abuse liability.

While proximal hamstring tears at the myotendinous junction are common sports-related injuries that are often successfully treated nonoperatively, complete avulsions from the origin on the ischial tuberosity are less common and better treated with surgical repair to prevent significant functional limitations and ongoing weakness. The diagnosis can be easily missed, leading patients to present several months after the initial injury. In addition, some patients decide on nonoperative management initially but later present requesting surgical intervention. The delayed cases are challenging due to often significant tendon retraction, making direct repair difficult if not impossible. Techniques using allograft and autograft reconstruction have been described for this clinical situation. This Technical Note describes the use of 2 Achilles tendon allografts fixed via 5 suture anchors to reconstruct a chronic complete avulsion injury of the proximal hamstring with >5-cm retraction.A cute strains of the hamstring muscle group are

No abstract

No abstract