The α7-nicotinic acetylcholine receptor (nAChR) has long been a procognitive therapeutic target to treat schizophrenia. Evidence on the role of this receptor in cognition has been lacking, however, in part due to the limited availability of suitable ligands. The behavior of α7-nAChR knockout (KO) mice has been examined previously, but cognitive assessments using tests with cross-species translatability have been limited to date. Here, we assessed the cognitive performance of α7-nAChR KO and wild-type (WT) littermate mice in the attentional set-shifting task of executive functioning, the radial arm maze test of spatial working memory span capacity and the novel object recognition test of short-term memory. The reward motivation of these mutants was assessed using the progressive ratio breakpoint test. In addition, we assessed the exploratory behavior and sensorimotor gating using the behavioral pattern monitor and prepulse inhibition, respectively. α7-nAChR KO mice exhibited normal set-shifting, but impaired procedural learning (rule acquisition) in multiple paradigms. Spatial span capacity, short-term memory, motivation for food, exploration and sensorimotor gating were all comparable to WT littermates. The data presented here support the notion that this receptor is important for such procedural learning, when patterns in the environment become clear and a rule is learned. In combination with the impaired attention observed previously in these mice, this finding suggests that agonist treatments should be examined in clinical studies of attention and procedural learning, perhaps in combination with cognitive behavioral therapy.

Patients with schizophrenia exhibit poor working memory (WM). Although several subcomponents of WM can be measured, evidence suggests the primary subcomponent affected in schizophrenia is span capacity (WMC). Indeed, the NIMH-funded MATRICS initiative recommended assaying the WMC when assessing the efficacy of a putative therapeutic for FDA approval. Although dopamine D1 receptor agonists improve delay-dependent memory in animals, evidence for improvements in WMC due to dopamine D1 receptor activation is limited. In contrast, the dopamine D2-family agonist bromocriptine improves WMC in humans. The radial arm maze (RAM) can be used to assess WMC, although complications due to ceiling effects or strategy confounds have limited its use. We describe a 12-arm RAM protocol designed to assess whether the dopamine D1-family agonist SKF 38393 (0, 1, 3, and 10 mg/kg) or bromocriptine (0, 1, 3, and 10 mg/kg) could improve WMC in C57BL/6N mice (n=12) in cross-over designs. WMC increased and strategy usage decreased with training. The dopamine D1 agonist SKF 38393 had no effect on WMC or long-term memory. Bromocriptine decreased WMC errors, without affecting long-term memory, consistent with human studies. These data confirm that WMC can be measured in mice and reveal drug effects that are consistent with reported effects in humans. Future research is warranted to identify the subtype of the D2-family of receptors responsible for the observed improvement in WMC. Finally, this RAM procedure may prove useful in developing animal models of deficient WMC to further assess putative treatments for the cognitive deficits in schizophrenia.

Background Keratoacanthomas (KAs) are neoplasms of squamous epithelium which exhibit rapid growth and are often difficult to distinguish clinically from squamous cell carcinoma. Excision is the most common treatment, but in refractory cases or for KAs in cosmetically sensitive areas, nonoperative modalities may be better suited. Objective To compare efficacies of topical and intralesional therapies for the treatment of KAs. Methods A systematic literature review was performed using Medline, Ovid, and Embase. Studies looking at the efficacy of topical or intralesional treatments for KAs were included. To compare efficacy, 2-tailed t-tests were performed, with P < .05 considered statistically significant. Results Forty-one studies were identified across 5 modalities. Both topical and intralesional treatments had high KA eradication rates (92%-100%). Intralesional 5-fluorouracil led to faster KA healing times when compared to intralesional methotrexate (3.7 vs 4.6 weeks, P = .017). Similarly, topical 5-fluorouracil led to faster time to heal than topical imiquimod (3.8 vs 7.6 weeks with imiquimod, P < .0001). Conclusion For nonoperative treatment of KAs, strong evidence currently exists for both topical and intralesional therapies. Decisions on which modality to use should be made on a case-by-case basis.

No abstract

No abstract