Berberine is an active chemical compound which has the ability to affect cognition and behavior. Berberine is a chemical which can be found naturally in many plants, but it is difficult to acquire adequate dosages through diet alone, so it is low in bioavailability.

Typically, berberine extracts are used in experimental settings and are ordered from pharmaceutical companies, in order to be applied to research. Scientifically, berberine is classified as an isoquinoline alkaloid and has been used clinically as an anti-inflammatory and anti-diabetic supplement.[1]

Berberine is increasingly becoming a well-studied and understood supplement with the potential to be extended into the realm of Neuropsychopharmacology. In fact, many findings have already been gathered with regards to how berberine offers positive benefits to the brain. For example, berberine is neuroprotective against ischemia due to its antioxidant properties.[1]

In this article we will review how berberine impacts behavior and cognition, mainly focusing on depression and memory-related animal models, and taking special consideration of which mazes are most effective at examining particular aspects of behavior.

Berberine Protects Against Stress-Induced Depression

Dysregulation of the hypothalamic-pituitary axis (HPA) is somehow associated with major depression and berberine has been shown to be able to intervene in this interaction. A healthy, normal reaction to stress involves the release of glucocorticoids into the bloodstream, a response which is regulated by the brain’s glucocorticoid receptors. Although glucocorticoids are protective in nature and regulate the organism’s efficient use of energy and material metabolism, the glucocorticoid regulatory function can be damaged by chronic stress. Many studies have shown a relationship between depressive symptoms, very high concentrations of glucocorticoids, and impaired neurogenesis in the hippocampus.

So, to assess the impact of berberine in this chronic-stress related form of depression, a group of scientists used behavioral assays to measure the performance of berberine-treated and non-treated mice which prior to experimentation went through induction of depression via corticosterone injections.

Some of the experimental animals were given berberine hydrochloride supplements which the researchers obtained from a pharmaceutical company. To measure behavior, a Forced Swim Test was given to all of the animals, a test which lasts for 6 minutes and begins by placing the animals in the middle of the water, thus forcing them to swim. The researchers began recording instances of immobility during the last 4 minutes of the test. Immobility is a behavior which is defined as the mouse floating in the water without making any movement or fuss, only exerting minimal motions, in order to keep the head suspended above water.[2]

The mice that were given corticosterone injections, thus inducing depression, had a significantly longer instance of immobility than the control group did, indicating a higher frequency of depressive-like behaviors by being immobile for a prolonged period of time. Interestingly, berberine treatment reduced immobility time in depressed mice, performing at the level of fluoxetine, a commonly distributed anti-depressant (commercially known as Prozac among other trade-names) which is a selective serotonin reuptake inhibitor.