Does motherhood dampen cocaine’s effects?

Mother rats respond much differently to cocaine than female rats that have never given birth, according to new University of Michigan research that looks at both behavior and brain chemistry.

The findings may help lay the groundwork for more tailored human addiction treatment, based on scientific understanding of how gender, hormones and life experience impact drug use.

In an oral presentation at the Society for Neuroscience meeting, U-M researcher Jennifer Cummings, Ph.D., summarized findings from experiments with rats at the Molecular and Behavioral Neuroscience Institute, part of the U-M Medical School. She worked with Jill Becker, Ph.D., of the U-M Department of Psychology.

They identified clear differences in how intensely the “pleasure centers” in the mother rats’ brains reacted to the drug, compared with non-mothers. Mother rats’ brains released less of a chemical called dopamine, which helps cause the “high” from cocaine.

They also found an interaction with stress: mother rats that were exposed to periods of increased stress weren’t willing to work as hard to get a dose of cocaine, compared with rats that had never given birth or mother rats that weren’t exposed to the stress – even though the stressed mother rats showed an increased tendency to use cocaine when it was easy to get.

Taken together, the findings suggest that the experience of becoming a mother alters a female’s overall response to cocaine – adding complexity to the issue of how best to treat addiction.

“While we have not yet identified a mechanism to explain these differences, they do suggest that the reward system and brain circuitry affected by cocaine is changed with maternal experience,” says Cummings, a research investigator at MBNI and former postdoctoral fellow in Becker’s laboratory. “The next step is to determine how factors such as hormone changes in pregnancy and early motherhood, and the experience of caring for offspring, might be differentially contributing to this response.”

Stony Brook Researchers Develop Neuroimaging Technique Capturing Cocaine’s Devastating Effect on Brain Blood Flow

Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal’s October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

In “Cocaine-induced cortical microischemia in the rodent brain: clinical implications,” the researchers discovered that cocaine administered in doses equivalent to those normally taken by abusers caused constriction in blood vessels that inhibited CBF for varying lengths of time. Brain arteries, veins, and even capillaries, the smallest vessels, were affected by the doses. CBF was markedly decreased within just two-to-three minutes after drug administration. In some vessels, a decrease in CBF reached 70 percent. Recovery time for the vessels varied. Cocaine interrupted CBF in some arteriolar branches for more than 45 minutes. This effect became more pronounced after repeated cocaine administration.

“Our study revealed evidence of cocaine-induced cerebral microischemic changes in multiple experimental models, and we were able to clearly image the process and vasoactive effects at a microvascular level,” said study Principal Investigator Yingtian Pan, PhD, Professor, Department of Biomedical Engineering, Stony Brook University. “These clinical changes jeopardize oxygen delivery to cerebral tissue making it vulnerable to ischemia and neuronal death.”

Morphine and cocaine affect reward sensation differently

A new study by scientists in the US has found that the opiate morphine and the stimulant cocaine act on the reward centers in the brain in different ways, contradicting previous theories that these types of drugs acted in the same way.

Morphine and cocaine both affect the flow of the neurotransmitter dopamine, which has been shown to be important in the feeling of reward. When a dopamine neuron is stimulated it releases dopamine, which is then taken up by neighboring cells. Any excess is reabsorbed into the original dopamine neuron by a process known as “reuptake.”

Cocaine is known to block reuptake, and the excess dopamine leads to an enhanced reward effect. Cocaine is also known to make the cells in the nucleus accumbens, which receives signals from the VTA, more sensitive to cocaine. It was already known a protein called brain-derived neurotrophic factor (BDNF) in the VTA region of the brain enhances the reward response to cocaine.

The new study shows that BDNF has the opposite effect when morphine is present, decreasing the reward response and the development of addiction rather than enhancing it. The researchers identified numerous genes regulated by BDNF and associated with its effects. They used genetic techniques to suppress BDNF, and then directly excited the neurons in the nucleus accumbens that normally receives transmitted impulses from the VTA.

They found that suppressing BDNF in the VTA allowed morphine to increase the excitability of dopamine neurons and hence enhance the reward. When they optically excited the dopamine terminals in the nucleus accumbens that normally receive the transmissions from the VTA, they also found a reversal in the normal effect of BDNF.

Scripps Research Institute Scientists Show Two-Drug Combination Has Potential to Fight Cocaine Addiction

A fine-tuned combination of two existing pharmaceutical drugs has shown promise as a potential new therapy for people addicted to cocaine—a therapy that would reduce their craving for the drug and blunt their symptoms of withdrawal.

In laboratory experiments at The Scripps Research Institute, the potential therapy, which combines low doses of the drug naltrexone with the drug buprenorphine, made laboratory rats less likely to take cocaine compulsively—a standard preclinical test that generally comes before human trials.

While the two-drug combination would have to prove safe and effective for people in clinical trials before approval by the U.S. Food and Drug Administration (FDA), the work represents a significant advance in the field because there are currently no FDA-approved medications for treating cocaine addiction.

The mechanism of action of cocaine

Cocaine modifies the action of dopamine in the brain. The dopamine rich areas of the brain are the ventral tegmental area, the nucleus accumbens and the caudate nucleus – these areas are collectively known as the brain’s ‘reward pathway’. Cocaine binds to dopamine re-uptake transporters on the pre-synaptic membranes of dopaminergic neurones. This binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by monoamine oxidase in the nerve terminal. Dopamine remains in the synaptic cleft and is free to bind to its receptors on the post synaptic membrane, producing further nerve impulses. This increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use.

Old beyond years. A 3D model of merged imaging scans shows the brain areas affected by age (blue) in healthy people (left) and longterm cocaine users (right). 

Credit: Karen Ersche/University of Cambridge

Full article: Cocaine may age the brain by Elizabeth Norton