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MRI study sheds light on zolpidem's effects on neurochemistry, study shows

Thursday, November 20 2008 | Comments

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What's This? By Kate Kahn

A new study suggested that acute administration of the nonbenzodiazepine hypnotic zolpidem in healthy individuals reduces thalamic GABA levels while increasing sedative and dysphoric effects.

Though behavioral effects of zolpidem are well documented, little is known about zolpidem's effects on brain chemistry in patients, the study authors noted. Dr.  Stephanie Licata and colleagues from McLean Hospital at Harvard Medical School utilized proton magnetic resonance spectroscopy (1H MRS) to measure the effects of zolpidem on brain chemistry.

In the single-blind, placebo-controlled study, the researchers gave zolpidem 10 mg to 19 healthy participants (7 men, 12 women) ages 21 to 35 years. Only drug-naive participants were included, reporting less than 10 lifetime recreational experiences with drugs of abuse, with the exception of alcohol. After zolpidem administration, participants underwent 1H MRS scanning at 4-Tesla. Investigators gathered neurochemical measurements from single voxels within the anterior cingulate cortex and the thalamus.

In addition, during the 1H MRS scan, participants answered a series of questionnaires that assessed subjective mood states associated with zolpidem treatment. Researchers also utilized sedation/intoxication scores and psychotomimetic/dysphoric scales of the Addiction Research Center Inventory to evaluate the effects of zolpidem.

While zolpidem did not affect GABA levels in the anterior cingulate cortex, zolpidem was associated with a reduction in GABA levels in the thalamus. In addition, the reduction in GABA levels was associated with patients reporting feeling "dizzy." The authors noted that this association may be the result of zolpidem's interaction with alpha 1GABAA receptors in the cerebellum and projecting vestibular information to the thalamus. They also suggested that cortical projections may also play a role.

Other subjective effects reported more frequently in the zolpidem group than in the placebo group included "nauseous," being "confused," and "bad effects" (P<.05). Similarly, the sedation/intoxication scores and psychotomimetic/dysphoric scores were significantly higher in the zolpidem group versus in the control group (P<.05).

The authors concluded that zolpidem reduces thalamic GABA levels and increases dysphoric effects.  (Program 58.25, Poster DD6)

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