An interview with Paola Maccioni, awarded a fellowship "L'Oreal Italia Per le Donne e la Scienza"

Paola Maccioni is a young researcher engaged in the study of alcohol-dependence. In Italy, the alcohol consumption is articulated from dramatic figures, continuously worsening.

News and statistics say that.

It is a serious social problem which reaps victims above all among the very young people, unaware of the damages that alcohol can provoke to the brain. This prize offers the occasion to remember it.

Q.: Paola Maccioni shows a visiting-card rich in merit and passion, as the stages preceding this acknowledgment reveal and which are told with pride and hope.

R.: I am graduated with honours in Biological Sciences more than three years ago at the University of Cagliari . Immediately after the bachelor, I began as a researcher at the Neuroscience Institute of the National Research Council (CNR) in Cagliari , with a fellowship. In the meantime, I have won the competition for a PhD position in Neuroscience at the University of Cagliari .

Q.: "L'Oréal Italia Per le Donne e la Scienza " in collaboration with the Italian National Commission UNESCO is at fifth edition. Judge Commission President Professor Umberto Veronesi. An important acknowledgment for a young researcher.

A.: Every year "L'Oréal Italia Per le Donne e la Scienza ", together with UNESCO, announces five 15.000 Euro fellowships for young Italian women researchers to promote and support their research in the laboratories where they already work. It is an Italian program of international respite and in these years it has given a prize to the job of more than 260 scientists in the world.

Q.: Dr.ssa Maccioni come to the research project won you this prize. A project started by a great scientist, Professor Gessa, well known in the scientific international community both for his scientific merits and quality of great orator. A project which carries on by discoveries of the promising and enthusiast researchers collecting ideas produced by that tradition.

A.: Since several years, the study of neurobiologic correlate of alcoholism - that is the alcohol mechanisms of action in the brain - and the possible identification of new drugs in alcoholism treatment is one of the main research project of the Neuroscience Institute CNR in Cagliari. This research line has been started various years ago by Professor Gian Luigi Gessa and has carried out the discovery of drugs, like acid gamma-hydroxybutyric acid (GHB), now used in alcoholism therapy. My research group is now directed by Giancarlo Colombo and includes noteworthy researchers, Mauro Carai, Carla Lobina and Claudia Cabras.

Q.: The neurobiologic mechanisms associated with alcoholism can not be studied in humans, for practical reasons more than ethics. Therefore it is important to characterize experimental models which are able to reproduce some aspects, at least, of the human condition.

A.: Historically, my research group, in their neurobiology and pharmacology studies of alcoholism, employs the bred Sardinian alcohol-preferring (sP) rats, one of the few strains in the world genetically selected because of their voluntary elevated alcohol consumption. In 1981 Professor Gessa started this rat sP selection which now has caught up 65 generations. Exposed to the standard, homecage two-bottle "alcohol vs water" choice regimen, the sP rats show a clear preference for the alcoholic solution daily assuming alcohol amount equivalent to one bottle of whisky for humans. These rats sP are a validated experimental model of alcoholism.

Q.: The alcohol, like other drugs of abuse, induces dependence through a motivational mechanisms that recruit well known accomplices. Is it possible to block their potential of abuse and the induction of dependence?

A.: GABA B receptors are one of the receptor type binding GABA, the main inhibitory neurotransmitter in the mammalian brain. The stimulation of GABA B receptors by GABA induces the inhibition of some cerebral neurons. Recent experimental evidence and following clinical studies, even if preliminary, demonstrate that pharmacological stimulation of GABA B receptors inhibits self-administration (in rats) and assumption (in humans) of various drugs of abuse, such as cocaine, heroin, nicotine and alcohol.

Q.: In your study you have used a positive allosteric modulator, GS39783, which acts on GABA B receptor showing anti-alcohol effects.

A.: The positive allosteric modulators are drugs which bind to the receptor, not directly activating it, but strengthening its function and facilitating binding of the endogenous neurotransmitter (or drugs called full agonists). In the case of GABA B receptor, baclofen is a full agonist, while GS39783 (that is the molecule that I am studying) is a positive allosteric modulator: both activate the function of GABA B receptor and reduce alcohol self-administration in alcohol-preferring rats, although with different mechanism. Our results demonstrate that the stimulation of GABA B receptor, both through full agonist, baclofen, and positive allosteric modulator, GS39783, suppresses acquisition and maintenance of alcohol drinking behavior in sP rats. This effect would be caused by the inhibition of dopaminergic cerebral system involved in alcohol rewarding effects.

Q.: Therefore the positive allosteric modulators of GABA B receptor could be used in clinical practice.

A.: Now, the only drug GABA B used in clinical experimentations is baclofen, a full agonist. The results obtained are very promising: they demonstrate a marked effectiveness in the suppression of alcoholic beverages assumption, craving for alcohol (that is a powerful urge to drink, or intense thoughts about alcohol) and abstinence syndrome in alcoholic. The positive allosteric modulators have not yet been tested in clinical practice because the toxicological experimentations that must precede every clinical study have not yet been conducted. For this reason the research with these drugs is now limited to the animal models.

Q.: The results of your research could be also important to understand the mechanisms of action of other drugs of abuse.

A.: Experimental studies carried out in other laboratories have demonstrated that GS39783, like baclofen, suppresses nicotine and cocaine self-administration in rats, confirming the capability of these drugs in the treatment of drug addiction.

Q.: Which are the next stages of your travel?

A.: I propose myself to extend the study of GS39783 effects to other aspects of the alcoholism using suitable experimental models to understand both the potentiality of this drug and the role of GABA B receptor in modulation of alcohol effects in the brain.

Q.: A great satisfaction for a young researcher, still more if woman. Paola Maccioni reserves the conclusion for the young Italian researchers, encouraging them with wise enthusiasm mixed to right amount of irony.

A.: This is a job that demands sacrifices, but it gets say to myself: "Thanks God is Monday!".

It's required an auspicious toast.

Marina Ferrario