modello per invio relazione di metà e fine periodo

MODELLO PER INVIO RELAZIONE DI METÀ E FINE PERIODO
NOME E COGNOME: ____LUISA PONZONI
UNIVERSITÀ: __UNIVERSITA’ DEGLI STUDI DI MILANO
DIPARTIMENTO (in caso di borsa per soggiorno all’estero specificare l’ente presso cui si è svolta la
ricerca): _DIP. DI BIOTECNOLOGIE MEDICHE E MEDICINA TRASLAZIONALE
TUTOR (in caso di borsa per soggiorno all’estero specificare il tutor dell’ente presso cui si è svolta la
ricerca): __DOTT.SSA MARIAELVINA SALA
TIPOLOGIA DI BORSA RICEVUTA: _BORSA DI STUDIO PER PROGETTI DI RICERCA IN AMBITO
FARMACOLOGICO BANDITA DALLA SIF GRAZIE AL CONTRIBUTO INCONDIZIONATO DI MSD ITALIA
TIPOLOGIA DI RELAZIONE (es.: metà periodo o finale): __RELAZIONE FINALE
TITOLO DELLA RELAZIONE: __ A NEW MOUSE MODEL TO STUDY THROUGH ELECTRONIC OR
CONVENTIONAL CIGARETTE SMOKE: I) NICOTINE DEPENDENCE AND ITS RELIEF WITH NEW NICOTINIC
PARTIAL AGONISTS; II) THE ALTERED SENSITIVITY TO REWARDING EFFECTS OF Δ9TETRAHYDROCANNABINOL (Δ9-THC)
RELAZIONE:
Cigarette use remains a serious public health issue. Besides, e-cigarettes (e-cig) are becoming
increasingly popular but so far only few studies are available on the effect of these devices.
In the first part of my project, I have validated a new mice model of smoke or e-cig exposure
(Ponzoni et al., 2015) that mimics the intermittence and route of nicotine administration in humans
simulating the unique pharmacokinetic characteristics (rate of absorption and brain delivery) that
are associated with smoking.
The results demonstrated that chronic intermittent exposure to tobacco smoke or e-cig vapour has
the same effects on nAChR up-regulation, brain nicotine and cotinine levels. Tobacco smoke leads
to more severe mecamylamine-precipitated withdrawal (WDW) and more evident cognitive deficit
24 hours after cessation whereas e-cig vapour elicits more severe anxiety. Finally data showed that
e-cig group elicits an early onset of a depressive-like behavior (at 60 days from nicotine WDW),
compared to cig-group (at 90 days from nicotine WDW).
Since difficulty of concentration is a symptom of nicotine WDW that may contribute to relapse in
individuals trying to quit smoking (Myers et al, 2013), my first aim was to evaluate possible
cognitive attentional deficits using the Virtual object recognition test, a new task recently validated
Da inviare a: Società Italiana di Farmacologia – e-mail: [email protected]; [email protected]
in my laboratory (Braida et al. 2013). This experiment demonstrated that tobacco smoke exposed
mice showed a worsened attentional deficit compared to e-cig exposed animals, starting from 24
hour to 60 days after exposure.
Notably, among adolescent tobacco smokers, who also smoke marijuana, the frequency of
marijuana use was associated with greater levels of nicotine addiction. Thus, importantly, while no
direct association between earlier onset of nicotine use and cannabis use disorders was found,
earlier nicotine use may indeed be of indirect relevance for cannabis use disorder risk (Chen et al.,
2005). My second aim was to verify whether cig smoke or e-cig vapour exposure facilitate the
subsequent reinforcing effects of Δ9-Tetrahydrocannabinol (THC) during short and long term
WDW and to do this, e-cig, cig and air exposed groups were submitted to Conditioned Place
Preference (CPP) task, using a dose which per se was not significantly rewarding, and evaluated
after 2, 30 and 60 days after exposure.
Cig smoke exposed mice exhibited increased rewarding effects to THC (0.01 mg/kg) compared to
air group. Also e-cig exposed animals exhibited a greater sensitivity to a low dose of THC
compared to controls, although less pronounced than tobacco smoke treated group. In both exposed
groups, THC increased sensitivity was most evident at 30 and especially at 60 days after nicotine
exposure.
These results demostrate that the nicotine WDW, after prolonged exposure, induces
neurobiochemical changes, a pathological emotional profile and an altered sensitivity to rewarding
effect of THC.
Legend
Fig. 1: A) Discrimination index evaluated in the Virtual Object Recognition task 1, 30 and 60 days
after cig, e-cig or air exposure; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs corresponding
air group; $P<0.05 vs corresponding e-cig group. B) Difference in the time spent in the drug-paired
compartement between POST and PRE conditioning period (Δ) in the CPP test evaluated 2, 30 and
60 days after withdrawal. ***P<0.001 vs corresponding vehicle, $$$$P<0.0001 vs THC 0.01 mg/kg
at 2 and 30 days, same exposure, &&&P<0.001 vs corresponding e-cig (Two way Anova,
Bonferroni test)
Da inviare a: Società Italiana di Farmacologia – e-mail: [email protected]; [email protected]
References
Ponzoni, Moretti, Sala, Fasoli, Mucchietto, Lucini, Cannazza, Gallesi, Castellana, Clementi, Zoli,
Gotti, Braida Different physiological and behavioural effects of e-cigarette vapour and cigarette
smoke in mice Eur Neuropsychopharmacol, 25(10):1775-86, 2015
Myers, Taylor, Salmeron, Waters, Heishman Nicotine enhances alerting, but not executive,
attention in smokers and nonsmokers Nicotine Tob Res, 15(1):277-81, 2013
Braida, Donzelli, Martucci, Ponzoni, Pauletti, Langus, Sala Mice discriminate between stationary
and moving 2D shapes: application to the object recognition task to increase attention Behav Brain
Res, 242:95-101, 2013
Chen, O'Brien, Anthony Who becomes cannabis dependent soon after onset of use?
Epidemiological evidence from the United States: 2000-2001 Drug Alcohol Depend, 79(1):11-22,
2005
Da inviare a: Società Italiana di Farmacologia – e-mail: [email protected]; [email protected]
Figure 1
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Da inviare a: Società Italiana di Farmacologia – e-mail: [email protected]; [email protected]