For many people, the thought of a tasty burger or a cold pint of beer conjures up a vivid mental image and drives behaviour. <\/p>\n
This link between thinking and doing serves a clear function \u2013 it motivates us to get the necessities for life. <\/p>\n
But for some, this process can malfunction. Preoccupation with these rewarding stimuli can lead to disorders of substance overuse, including overeating to the point of obesity and alcohol abuse. <\/p>\n
Studies going back to the 1970s<\/a> have linked vivid mental imagery with drug abuse<\/a>.<\/p>\n Understanding this link between craving and consuming is central to understanding addiction. This has eluded neuroscience for decades, but the introduction of a new class of drugs for weight loss may have given us just the lever we need to understand it.<\/p>\n These new drugs \u2013 including Ozempic and Wegovy \u2013 mimic the GLP-1 hormone to stimulate insulin release, slow digestion, and increase feelings of fullness. They are known as GLP-1 agonists and were originally used to treat type 2 diabetes because they help control blood sugar<\/a>. <\/p>\n As a side effect, people using these drugs also lost a lot of weight, in some cases almost as much as might be expected from bariatric surgery<\/a>. <\/p>\n But there is another less well publicised effect. Human studies show that GLP-1 agonists reduce alcohol consumption<\/a>. Preclinical animal studies suggest these drugs also reduce the use of cocaine<\/a>, amphetamines<\/a>, opiates<\/a> and nicotine<\/a>. <\/p>\n These drugs are changing how we think about the brain\u2019s reward system. They may also open new treatment options for obesity, alcohol dependence and the consumption of other addictive substances.<\/p>\n How the brain regulates reward stimuli<\/p>\n We have a reasonable understanding of the brain\u2019s \u201creward circuitry\u201d associated with regions that produce the neurotransmitter dopamine. <\/p>\n These brain parts \u2013 the ventral tegmental area (VTA<\/a>) and nucleus accumbens (NAc<\/a>) \u2013 have been the subject of research on reward for decades. They are the obvious candidate regions to look for a mechanism for GLP-1 action in the brain. But they lack significant density of receptors for GLP-1<\/a> and are unlikely to be the direct mechanism. <\/p>\n We must, therefore, consider other brain regions to understand the anti-consumption effect of GLP-1 drugs. <\/p>\n One jump \u201cupstream\u201d from the dopamine-producing brain parts is a region called the lateral septum. This brain structure has been historically implicated in emotional regulation. <\/p>\n Back in 1953, pioneering US behavioural researchers Joseph Brady and Walle Nauta coined the term \u201cseptal rage<\/a>\u201d when animals with damage in the lateral septum showed increased aggression<\/a>, while direct stimulation of this brain region reduced aggression<\/a>. <\/p>\n Much more recent work<\/a> has placed the lateral septum at the centre of a neural connectivity network. This has reframed how we think about its function. <\/p>\n While a link between the lateral septum and another region called the hypothalamus is probably responsible for septal rage, the lateral septum links with many other regions with various functions<\/a>.<\/p>\n The brain\u2019s reward control centre<\/p>\n The lateral septum inherits much of its primary input from a brain region called the hippocampus. <\/p>\n This region is well known as the place that lets us form long-term \u201cepisodic memories<\/a>\u201d. A famous case of hippocampal damage, Henry Molaison (patient HM), was unable to form new memories after his surgery for epilepsy. He effectively lived without a past, in permanent present tense<\/a>. <\/p>\n The hippocampus also contains the remarkable \u201cplace cells\u201d \u2013 neurons that fire corresponding to a person\u2019s thoughts about their position in space<\/a> and, as recent research<\/a> has shown, time. <\/p>\n This \u201cwhere and when am I\u201d information gets forwarded to the lateral septum. Key research has recently shown the lateral septum also contains place cells, but these cells strongly respond to rewards<\/a>. They effectively add \u201cwhat is good in this place\u201d to the \u201cwhere and when am I\u201d information from the hippocampus. <\/p>\n Critically, the lateral septum shares this information with the dopamine-producing regions we would normally associate with reward. <\/p>\n Neuroscientists now think of the lateral septum as the brain region that lets us \u201cthink about\u201d rewards \u2013 our conscious perception of them \u2013 and communicates with the machinery in the brain\u2019s reward system that produces dopamine to make us feel good about them.<\/p>\n There is one last reason to suspect the lateral septum as the mechanism behind the anti-consumption effect of GLP-1 agonists. It is absolutely loaded with GLP-1 receptors<\/a>. <\/p>\n Emerging research points to this as the mechanism. GLP-1 activation directly in the lateral septum has recently been shown to reduce food consumption in mice<\/a>. Earlier this year, another study showed the same for alcohol consumption<\/a>. <\/p>\n