Attention

Overall Dependence Syndrome encompasses a range of reinforcing behaviors and physiological responses related to addiction, but its defining features are not strictly tolerance, withdrawal, and dependence as these are not universally applicable to all addictions.

Svanberg (2018) notes that tolerance, withdrawal, and dependence, while commonly associated with certain drugs and behaviors, should not be seen as the central defining factors of addiction.

**Focus 8.1: The ‘Addicted Brain’ **
- Research by Nestler and Malenka (2004), and Solis (2013) highlights how drugs elevate the brain's reward system.
- The reward system, a complex network of neurons, evolved to evoke feelings of pleasure, similar to those felt after eating or during sexual activities, thereby promoting behaviors that induce pleasure.
- Chronic drug use leads to structural and functional changes in neurons within this system that can persist long after drug use has ceased.

A crucial part of this reward circuit involves the pathway from the ventral tegmental area (VTA), rich in dopamine-producing neurons, extending to dopamine-sensitive neurons in the nucleus accumbens (NA), located beneath the frontal cortex.
- These changes in neuron structure and function significantly contribute to the mechanisms of tolerance and dependence, along with the cravings prompting repeated drug use and potential relapses following periods of abstinence.

The VTA communicates with various limbic brain regions through the medial forebrain bundle, including:
- Nucleus Accumbens (NA)
- Amygdala
- Prefrontal Cortex (PFC)
- Collectively, these structures form the ‘common reward pathway’ that influences pleasurable sensations and reinforcement of behaviors.

Additional paths connect the NA and VTA to other brain areas, heightening sensitivity to cues associated with past drug use (e.g., drug paraphernalia, places of use), which may trigger relapses, particularly under stress.

The VTA–NA connection functions as a ‘rheostat of reward’:
- It signals other brain centers regarding the level of reward produced by various activities. Higher reward impressions increase the likelihood of an organism remembering and repeating the pleasurable experience.

fMRI and PET scans indicate that in the brains of cocaine addicts, the NA shows increased activity when:
- Presented with cocaine (e.g., offered a snort).
- Shown videos of cocaine use.
- Displayed images related to cocaine use (e.g., a photograph of white lines on a mirror).
Brain areas like the amygdala and some cortical regions also show responses to these stimuli.
- During scanning, participants often rate their feelings of rush and craving on a scale of 0-3.
Studies indicate:
- (a) The VTA and sublenticular extended amygdala are crucial for the rush induced by cocaine.
- (b) The amygdala and NA contribute to both the cocaine's rush and the craving that escalates as the initial euphoria diminishes, as depicted in related figures.

Evidence suggests similar brain responses occur in compulsive gamblers when exposed to images of slot machines, indicating a broader applicability of addiction mechanisms across different behaviors.

Addiction alters crucial molecular processes at synapses, especially impacting the connection between the PFC (involved in decision-making) and the NA (linked to habit formation), which complicates the ability to change habitual routines.
- Synapses become rigid, unable to adjust to new information such as the desire to cease drug use.
The neurotransmitter glutamate plays a key role in the normal flexibility of synaptic connections.
- Drug use disrupts glutamate-related processes.
Glial cell protein pumps responsible for stabilizing glutamate levels in the extracellular space become dysfunctional due to drug use, further complicating addiction.

Adolescents are particularly at risk for addiction as their PFC is still maturing:
- The PFC is critical for inhibitory control and working memory, which are essential for decision-making and resisting impulses to use substances.