Posts tagged drugs

March 8, 2012

The left image shows GABA inhibitory neurons (labeled green) in the brain’s reward pathway. The right panel shows electrical activity of GABA inhibitory neuron in a saline-injected or methamphetamine (METH)-injected mouse. Activation of the GABA type B receptor normally silences electrical activity, but has no effect in a mouse 24 hours after a single injection of methamphetamine Credit: Courtesy of Kelly Tan and Claire Padgett, Salk Institute for Biological Studies

A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research by scientists at the Salk Institute for Biological Studies.

Their findings, reported March 7 in Neuron, suggest this powerful reaction to the drug assault may be a protective, anti-addiction response. The scientists theorize that it might be possible to mimic this response to treat addiction to these drugs and perhaps others, although more experiments are required to explore this possibility.

"It was stunning to discover that one exposure to these drugs could promote such a strong response that lasts well after the drug has left the body," says Paul Slesinger, an associate professor in the Clayton Foundation Laboratories for Peptide Biology. "We believe this could be the brain’s immediate response to counteract the stimulation of these drugs."

Read more …

Decreased cerebral blood flow (CBF) after psilocybin imaged by fMRI. Regions where there was significantly decreased CBF after psilocybin versus after placebo are shown in blue. No CBF increases in any region were observed. Image Copyright © PNAS, doi:10.1073/pnas.1119598109

(Medical Xpress) — Psychedelic substances have long been used for healing, ceremonial, or mind-altering subjective experiences due to compounds that, when ingested or inhaled, generate hallucinations, perceptual distortions, or altered states of awareness. Of these, the psychedelic substance psilocybin, the prodrug (a precursor of a drug that must in vivo chemical conversion by metabolic processes before becoming an active pharmacological agent) of psilocin (4-hydroxy-dimethyltryptamine) and the key hallucinogen found in so-called magic mushrooms, is widely used not only in healing ceremonies, but, more recently, in psychotherapy as well – but little has been known about its specific activity in the brain.

Recently, however, scientists in the Neuropsychopharmacology Unit at Imperial College London used complementary blood-oxygen level dependent (BOLD) functional MRI, or fMRI, in conjunction with a technique for imaging the transition from normal waking consciousness to the psychedelic state. The study found decreased blood flow and BOLD in the thalamus, anterior and posterior cingulate cortex, and medial prefrontal cortex. The researchers concluded that the surprising results strongly suggest that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.

Lead researcher Dr. Robin L. Carhart-Harris, working in the Neuropsychopharmacology Unit created by Prof. David J. Nutt, recounts the team’s main challenges in establishing an fMRI methodology that would be specific enough to highly correlate neurophysiological activity with the neuronal presence or absence of psilocybin. “There were a number of considerations,” Carhart-Harris tells Medical Xpress. “In terms of experimental design, we had to determine the precise dose and delivery protocol that would be appropriate for obtaining clear fMRI results. “For example,” he explains, “we had to consider temporal dynamics: If the drug was administered orally, the protracted period of time between ingestion, metabolism, and crossing of the blood-brain barrier would fall outside of the short scanning window needed to capture induced brain activity.” They therefore had to rely on intravenous administration.

Read more …