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Study the mechanisms of action of cocaine base paste

CONICET researchers administered paco to a group of mice and evaluated their effects at both behavioral and brain levels.
Science
07 September, 2019

Cocainebase paste(PBC) -also known asPaco — is an illegal abuse drug that mixes an unpurified extract of coca leaves with other alkaloids, in a combination that is generated as a natural result of the same extraction process . In addition to being a product derived from the manufacture of cocaine, paco produces among its consumers a clinical picture very different from that observed among cocaineusers, which would indicate that its mechanisms of action are also different.

According to specialists, PBC, in addition to being more addictive and toxic, induces among its consumers a more pronounced abandonment of social norms along with serious psychological disorders manifested in the form of cognitive impairment and impulsive and aggressive antisocial behavior.

Probably because it is a drug mostly used by adolescents and young people in Latin America — where it is located only behind marijuana and cocaine in the amount of consumption — its study so far has not attracted much interest among European and American scientists, which is why it is essential that researchers from countries such as Argentina are engaged in analyzing their effects and mechanisms of action.

In view of this need, a team of CONICETscientists at the Institute of Biological Chemistry of the Faculty of Exact and Natural Sciences (IQUIBICEN, CONICET-UBA) headed by Eduardo Cánepa, principal researcher of CONICET and director of the Laboratory of Neuroepigenetics and Early Adversity (FCEN, UBA), seeks to study the effects of Paco both at the behavioral level and the central nervous system by experimenting with animal models.

“ Although it is known that the effects of the Paco are devastating, it is not so much that is known so far about the mechanisms of action that mediate these consequences. To try to understand them, in this paper we use as an animal model a group of mice to which we administer PBC for 10 days in a row,” says Cánepa, referring to a recent paper published in the specialized journal,Psychopharmacology.

The researchers sought to see what was going on with this group of mice, on the one hand – at the behavioral level – regarding nervous type behavior, locomotion and memory, and on the other – at the molecular level – in relation to early expression genes in two regions of the brain: the prefrontal cortex and the nucleus accumbens.

“ What we did was administer paco to a group of mice for 10 days in a row and then we suspended the supply for the same period of time. Both during the period of chronic administration of the drug and after the end of the withdrawal period, mice were subjected to two standardized tests in the literature to measure locomotive activity and anxious-type behavior. At the same time, we control memory at the end of the chronicity period and at the end of abstinence,” saysBruno Berardino, CONICET postdoctoral fellow at IQUIBICEN and one of the first authors of the work.

In terms of locomotive activity and anxious-type behavior — so called because anxiety itself is a human disorder, which among drug users is sometimes what determines that patterns of addiction are generated — researchers recorded a noticeable increase during the period of chronic administration of PBC, as well as that high levels were maintained after ten days of abstinence.

“ In this respect, after a lapse without consumption of paco, the levels of anxiety and locomotive activity remain high. This tells us that the deterioration produced by this drug is very intense and

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