Quantitative analysis of performance on a progressive-ratio schedule: effects of reinforcer type, food deprivation and acute treatment with Δ⁹-tetrahydrocannabinol (THC)

Rats’ performance on a progressive-ratio schedule maintained by sucrose (0.6 M, 50 μl) and corn oil (100%, 25 μl) reinforcers was assessed using a model derived from Killeen’s (1994) theory of scheduled-controlled behaviour, ‘Mathematical Principles of Reinforcement’. When the rats were maintained at 80% of their free-feeding body weights, the parameter expressing incentive value, a, was greater for the corn oil than for the sucrose reinforcer; the response-time parameter, δ, did not differ between the reinforcer types, but a parameter derived from the linear waiting principle (Tₒ), indicated that the minimum post-reinforcement pause was longer for corn oil than for sucrose. When the rats were maintained under free-feeding conditions, a was reduced, indicating a reduction of incentive value, but δ was unaltered. Under the food-deprived condition, the CB1 cannabinoid receptor agonist Δ⁹-tetrahydrocannabinol (THC: 0.3, 1 and 3 mg kg-1) increased the value of sucrose; none of the other parameters was affected by THC. The results provide new information about the sensitivity of the model’s parameters to deprivation and reinforcer quality, and suggest that THC selectively enhances the incentive value of sucrose

Type II Keratins Are Phosphorylated on a Unique Motif during Stress and Mitosis in Tissues and Cultured Cells

Epithelial cell keratins make up the type I (K9–K20) and type II (K1–K8) intermediate filament proteins. In glandular epithelia, K8 becomes phosphorylated on S73 ((71)LLpSPL) in human cultured cells and tissues during stress, apoptosis, and mitosis. Of all known proteins, the context of the K8 S73 motif (LLS/TPL) is unique to type II keratins and is conserved in epidermal K5/K6, esophageal K4, and type II hair keratins, except that serine is replaced by threonine. Because knowledge regarding epidermal and esophageal keratin regulation is limited, we tested whether K4–K6 are phosphorylated on the LLTPL motif. K5 and K6 become phosphorylated in vitro on threonine by the stress-activated kinase p38. Site-specific anti-phosphokeratin antibodies to LLpTPL were generated, which demonstrated negligible basal K4–K6 phosphorylation. In contrast, treatment of primary keratinocytes and other cultured cells, and ex vivo skin and esophagus cultures, with serine/threonine phosphatase inhibitors causes a dramatic increase in K4–K6 LLpTPL phosphorylation. This phosphorylation is accompanied by keratin solubilization, filament reorganization, and collapse. K5/K6 LLTPL phosphorylation occurs in vivo during mitosis and apoptosis induced by UV light or anisomycin, and in human psoriatic skin and squamous cell carcinoma. In conclusion, type II keratins of proliferating epithelia undergo phosphorylation at a unique and conserved motif as part of physiological mitotic and stress-related signals