Al­co­hol, nico­tine re­shape the brain for ad­dic­tion

Study finds use can al­ter re­ward cen­ters, re­sult­ing in sus­cep­ti­bil­ity to co­caine

Baltimore Sun Sunday - - NEWS - By Melissa Healy

The idea of a “gate­way drug” may sound like a throw­back to the “Just say no” era. But new re­search of­fers fresh ev­i­dence that al­co­hol and nico­tine — two psy­choac­tive agents that are le­gal, ubiq­ui­tous and widely used dur­ing ado­les­cence — ease the path that leads from ca­sual co­caine use to out­right ad­dic­tion.

About 21 per­cent of those who use co­caine on an oc­ca­sional ba­sis wind up tak­ing the drug com­pul­sively, ex­perts es­ti­mate. That leads re­searchers who study drug ad­dic­tion to ask: What sets those ad­dicts apart from their peers? Per­haps al­co­hol and nico­tine are the miss­ing link.

When rats were primed with ei­ther sub­stance, they ex­pe­ri­enced durable chem­i­cal changes in their brains that could make them more sus­cep­ti­ble to co­caine de­pen­dency, ac­cord­ing to a study pub­lished last week in Science Ad­vances. Those changes were etched into the ma­chin­ery that turns genes on and off in the re­ward cen­ters of the brain, cre­at­ing a “per­mis­sive en­vi­ron­ment” for ad­dic­tion, the study au­thors wrote.

In­deed, when rats were al­lowed to drink al­co­hol ev­ery day for nearly two weeks — a con­sid­er­able length of time in the life­span of a rat — and then given ac­cess to a dose of co­caine, they en­gaged in drug-seek­ing be­hav­ior with such de­ter­mi­na­tion that they were barely de­terred by painful elec­tric shocks.

The ex­per­i­men­tal re­sults help “ce­ment the va­lid­ity of the gate­way hy­poth­e­sis,” said Dr. Nora Volkow, di­rec­tor of the Na­tional In­sti­tute on Drug Abuse, which funded the study.

The find­ings also sug­gest that re­searchers might be bet­ter off fo­cus­ing on “gate­way mech­a­nisms” — the com­mon molec­u­lar path­ways through which some sub­stances can in­flu­ence fu­ture ad­dic­tion — than on “gate­way drugs,” she added.

To be sure, even rats who had never tried al­co­hol took to co­caine when given the chance, press­ing a lever to ad­min­is­ter them­selves doses. And as re­searchers made rats work harder for a dose of co­caine, both tee­to­talers and al­co­hol-primed rats stepped up their ef­forts. Many rats con­tin­ued to press the lever — even when do­ing so re­sulted in in­creas­ingly stronger elec­tri­cal shocks. But al­co­hol made a big dif­fer­ence. In ex­per­i­ments led by psy­chi­a­trist Dr. Ed­mund Grif­fin, neu­ro­bi­ol­o­gist Dr. Eric R. Kan­del and epi­demi­ol­o­gist Denise Kan­del, all of Columbia Univer­sity, a group of rats were al­lowed ac­cess to al­co­hol for two hours a day over 11 days. Then they gained ac­cess to co­caine for var­i­ous stretches over the next 32 days.

As re­searchers re­quired more work for the co­caine, the al­co­hol-treated rats pressed a lever an av­er­age of 563 times — much more than the av­er­age 310 lever presses mus­tered by an­other group of rats with no al­co­hol his­tory. Days af­ter co­caine ad­min­is­tra­tion had ceased, the rats ex­posed to al­co­hol pressed the co­caine lever 58 times, on av­er­age — far more than the 18 lever presses av­er­aged by the rats that were not primed with al­co­hol, ac­cord­ing to the study.

The two groups of an­i­mals also re­acted dif­fer­ently to the painful shocks meant to de­ter them from us­ing co­caine. Among rats who’d got­ten no al­co­hol, the shocks prompted most to stop press­ing the lever pretty quickly, with only 14 per­cent con­tin­u­ing to do so. How­ever, among rats primed with al­co­hol, most were will­ing to en­dure sev­eral sets of shocks be­fore giv­ing up, and 29 per­cent con­tin­ued to press the lever even when do­ing so brought on the strong­est shocks re­searchers gave.

Re­searchers ob­served a wide range of chem­i­cal dif­fer­ences in their brains. Many of those changes were seen in­side the nu­cleus ac­cum­bens, a key node in the brain’s re­ward-seek­ing net­work. And they took place in the epigenome, the chem­i­cal mes­sag­ing sys­tem that turns genes on and off in re­sponse to chang­ing needs or cir­cum­stances.

Sci­en­tists had seen that when the spe­cific brain changes wrought by al­co­hol were in­duced by other means, the re­sult was a higher propen­sity to ad­dic­tion. The re­sults of ear­lier work by the same re­search group show that nico­tine use can, too.

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