Social isolation increases addiction vulnerability

Research carried out at The University of Texas at Austin (UT Austin) and reported this week in the journal Neuron has found that rats isolated during their adolescence are more vulnerable to amphetamine and alcohol addiction than those housed in groups. The research also discovered that the isolated rodents found addiction to amphetamines more difficult to overcome, and that these effects persisted even after they were reintroduced to a group.

Lead author Dr Leslie Ramsey Whitaker, formerly a doctoral candidate in Dr Hitoshi Morikawa’s laboratory at UT Austin, is now a postdoctoral fellow at the United States’ National Institute on Drug Abuse (NIDA). Dr Whitaker provided ScienceOmega.com with more detail about the background to the study and how it could influence efforts to prevent and treat addiction in humans, especially young adults.

"There have been decades of research on the behavioural effects of social isolation, in particular during the adolescent critical period that we refer to in the paper," Dr Whitaker began. "There are impairments in spatial learning and memory, increases in aggressive behaviour, and the animals appear to be more anxious, with deficits in social behaviour, as one might expect."

There have not been, however, many efforts to characterise the neurobiological basis or bases of the alterations that have been observed behaviourally. Some studies that have shown impaired neural plasticity in hippocampus – the brain region important for spatial learning and conscious memory – following social isolation, but the kind of memory at work in addiction is unconscious, Dr Whitaker has argued. The focus of this paper was, therefore, on the ventral tegmental area (VTA) which contains dopaminergic neurons and is associated with the brain’s reward system.

"Regarding alterations in reward learning that are relevant to addiction, several studies have found altered levels of dopamine and dopamine receptor expression in VTA target structures, but hardly any studies have directly examined the effects of isolation on the function of the dopamine neurons themselves," Dr Whitaker elaborated. "I believe we are the first to examine the effects of social isolation on synaptic plasticity in the VTA."

The 21 day old rats which were isolated for a period of 30 days – the equivalent of early and mid adolescence in humans – exhibited the tendency to be drawn to the small box where they received a dose of alcohol or amphetamines much more quickly than peers which had never been isolated. They showed a preference after just one exposure to a drug, compared to the repeated exposures required to condition the majority of group-housed rats.

Although the researchers examined the effects of isolating the animals at a slightly later point in their development, from 42 to 63 days old instead of 21 to 42, they did not find the same effects on neural plasticity or behaviour. They also looked at a slightly earlier time point, isolating the rodents for a shorter period of time when they were between 21 and 28 days old.

"Again, we saw no evidence of neural or behavioural alterations," Dr Whitaker related. "So it appears that the isolation is most damaging when it is long-term – three weeks or longer – and when it begins in the early adolescent period. Early to mid adolescence seems to represent a critical period during which isolation exerts its effects."

Addictive drugs such as amphetamines or alcohol trigger the release of dopamine, which is most often associated with feelings of pleasure, but Dr Horikawa has made the case for it to be considered a learning transmitter. Rather than associating the drug with pleasure or relief, it may be that the environmental, behavioural or physiological stimuli present when dopamine is released come to be associated more generally with a rewarding experience.

I asked Dr Whitaker why she thinks social isolation has the effect that it does in making rats so much more vulnerable to addiction and making that addiction notably harder to extinguish.

"I can't say for sure, but we think that isolated animals generally have fewer relevant inputs, social and environmental or otherwise," she responded. "Thus, when an interesting stimulus comes along – in this case, exposure to amphetamine or ethanol – they assign greater value to and learn more quickly and more permanently about cues or contexts associated with that stimulus." 

Social isolation in rodents is frequently used as a model of negative life experience, since the reaction that humans have to experiences of neglect, maltreatment and isolation is very similar. Humans who have had such experiences early in life are more likely to experiment with drugs and alcohol and more likely to become addicted.

These findings reinforce the fact that there is a neurobiological basis for behaviour, and alterations in brain function translate to alterations in behaviour.

"We were able to demonstrate a direct effect of an external, environmental manipulation on the function of dopamine neurons and their propensity for NMDA receptor plasticity," reiterated Dr Whitaker. "Our behavioural experiments also show that isolated animals, even after a single exposure to the drug, have an altered response profile that makes them more prone to addiction."

Although isolated lab rats are not directly equivalent to young people, the implications for human children are not hard to imagine. As well as being more likely to experiment with and become addicted to alcohol and other drugs, there is the possibility that other types of reward – such as food – could become associated with dopamine release in adolescents going through negative experiences. In the future, Dr Whitaker said, scientists may be able to manipulate rodent test subjects in the opposite manner, exposing them to an enriched, socially stimulating environment to test the idea that this might make them more resistant to addiction.

"I think it's important to explore non-pharmacological treatment options for addiction, so the idea of manipulating environmental factors to reduce addiction vulnerability in rodents is a step toward that goal," she added.