Franco Borsini

Bio: Franco Borsini is an academic researcher from Sigma-Tau. The author has contributed to research in topics: Agonist & Receptor. The author has an hindex of 38, co-authored 149 publications receiving 6057 citations. Previous affiliations of Franco Borsini include University of Pisa & Boehringer Ingelheim.

Is the forced swimming test a suitable model for revealing antidepressant activity

Abstract: The forced swimming test is reviewed. This test appears to be suitable for detecting antidepressant activity in rats but not in mice. Difference in experimental procedure may account for the different sensitivity to drugs of the two animal species.

Do animal models of anxiety predict anxiolytic-like effects of antidepressants?

Abstract: Chronically administered antidepressant drugs, particularly selective serotonin (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of all anxiety disorders, while the clinical effectiveness of "traditional" anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety disorder or acute panic attacks. This implies that animal models of anxiety should be sensitive to SSRIs and other antidepressants in order to have predictive validity. We reviewed the literature on the effects of antidepressants in the so-called animal models of anxiety and found that only the isolation-induced calls in guinea-pig pups may reveal anxiolytic-like action of all antidepressant classes after acute administration. Some other models, such as marble-burying or conditioned-freezing behaviours, and isolation- or shock-induced ultrasonic vocalisation models, may detect anxiolytic-like activity of acutely administered antidepressants, although the sensitivity of these models is usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive validity of models of "anxiety", such as the plus-maze and light–dark transition tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs. Far less work has been done on chronic administration of antidepressants in animal anxiety models. Unless and until such studies have been undertaken, the true predictive value of the anxiety models will remain unknown.

Animal models of depression in drug discovery: a historical perspective.

Abstract: Over the course of the last 50 years many models of major depressive disorder have been developed on the basis of theoretical aspects of this disorder. These models and procedures have been crucial in the discovery and development of clinically-effective drugs. Notwithstanding, there is presently great concern about the discrepancy between positive outcomes of new candidate drugs in animal models and apparent lack of efficacy in humans i.e., the predictive validity of animal models. Some reasons for this concern lie in the over-reliance in the face value of behavioural models, design of clinical trials, placebo responses, genetic variations in response to drugs, species differences in bioavailability and toxicology, and not least, disinterest of pharmaceutical sponsors to continue developing certain drugs. Present model development is focusing on endophenotypic aspects of behaviours rather than trying to model whole syndromes. This essay traces the origins and theoretical bases of our animal models of depression or depressed-like behaviours in humans and indicates how they have evolved from behavioural assays used to measure the potency and efficacy of potential candidate drugs to tools by which endophenotypes of depression may be identified and verified pharmacologically. A cautionary note is included though to indicate that the true predictive validity of our models will not be fully assessed until we can determine the attrition rate of molecules discovered from new drug targets translating into clinically-effective drugs.

The distinct role of medium spiny neurons and cholinergic interneurons in the D₂/A₂A receptor interaction in the striatum: implications for Parkinson's disease.

Abstract: A(2A) adenosine receptor antagonists are currently under investigation as potential therapeutic agents for Parkinson's disease (PD). However, the molecular mechanisms underlying this therapeutic effect is still unclear. A functional antagonism exists between A(2A) adenosine and D(2) dopamine (DA) receptors that are coexpressed in striatal medium spiny neurons (MSNs) of the indirect pathway. Since this interaction could also occur in other neuronal subtypes, we have analyzed the pharmacological modulation of this relationship in murine MSNs of the direct and indirect pathways as well in striatal cholinergic interneurons. Under physiological conditions, endogenous cannabinoids (eCBs) play a major role in the inhibitory effect on striatal glutamatergic transmission exerted by the concomitant activation of D(2) DA receptors and blockade of A(2A) receptors in both D(2)- and D(1)-expressing striatal MSNs. In experimental models of PD, the inhibition of striatal glutamatergic activity exerted by D(2) receptor activation did not require the concomitant inhibition of A(2A) receptors, while it was still dependent on the activation of CB(1) receptors in both D(2)- and D(1)-expressing MSNs. Interestingly, the antagonism of M1 muscarinic receptors blocked the effects of D(2)/A(2A) receptor modulation on MSNs. Moreover, in cholinergic interneurons we found coexpression of D(2) and A(2A) receptors and a reduction of the firing frequency exerted by the same pharmacological agents that reduced excitatory transmission in MSNs. This evidence supports the hypothesis that striatal cholinergic interneurons, projecting to virtually all MSN subtypes, are involved in the D(2)/A(2A) and endocannabinoid-mediated effects observed on both subpopulations of MSNs in physiological conditions and in experimental PD.

Neuroscience 細胞死：最近の知見

Abstract: 中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Vanilloid (Capsaicin) Receptors and Mechanisms

Abstract: Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and