Researchers attempt to make animals addicted to drugs, in order to better understand the neuroscience of drug addiction.

It didn't go so well with rats and cocaine...

Why do only a few people transition into being drug-addicted?

As a result of the limitations in spatial and temporal brain imaging, the origin, nature and casual effectiveness of cortical changes are largely unknown

"Mental Disorder" - A harmful behavioural or psychological condition that reflects an underlying dysfunction in the individual, particularly in its brain. ADD: that conflicts with society's expectable response

A heroin-withdrawn baby born from a mother addicted to heroin is physically dependent, but not dependent on heroin. (O'Brien 2011)

People may take drugs out of functionality, rationality and of their own will, rather than out of compulsion.

Harder than it seems

The idea of making a rat addicted to cocaine, then comparing its neuropathological alterations to a normal rat ... isn't that simple.

It has also been unable to lead to any significant translational impact for both medical diagnosis and treatment

For animals to be considered as having an addiction-like behaviour, they must be self-administering, and develop/present an array of changes that display important behavioural features of addiction

Ahmed and Koob 1998

Two groups of rats were given access to cocaine, one group for 1 hr, the other for 6+ hours a day. Those in the extended time session injected more doses over time.

  • Escalate cocaine intake
  • Work harder
  • Accept increased costs to obtain the drug
  • Became more vulnerable to stress
  • Higher tendency to reinstate their intoxication after extinction

Those in the extended group, when exposed to footshocks, resumed consuming the cocaine faster than the control group - difficulty in abstaining

  • Deceased neurocognitive functions
  • Long term drug users addicted to cocaine had deficits in neurocognitive functionality - generally mild in severity
    • Those in the limited access time had near-indistinguishable cognitive differences from drug-naive rats (without)
  • However, rats with extended access to cocaine showed reduce motor impulsivity in high-impulsive rats

Rat: Cocaine SA vs Alternate Non-drug Activities

If rats prefer to self-administer cocaine despite the opportunity of making a different choice,t hen one has ground to hypothesise a state of addiction that could then be confirmed by increasing the costs associated with drug preference

Test Condition 1 & 2

One lever rewarded a reward (cocaine or sacharin)
The other level was unrewarded

Test Condition 3

One lever rewarded cocaine
One level rewarded saccharin

Results

The preference of cocaine emerged more slowly than saccharin, indicative that cocaine is less reinforcing than saccharin.

After the stabilisation of preference, the time taken to choose cocaine was greater than the time taken to choose the saccharin - Rats may have been exercising voluntary abstinence, in the hope of receiving saccharin instead

Followup

After increasing the cocaine dosage from 0.25mg to 1.5mg per infusion, rats still preferred the saccharin reward (Lenoir et al 2007) - this indicates that the value of cocaine was bounded with a maximum that was lower than the value of the saccharin.

Behavioural Inertia

Maybe rats preferred saccharin because they grew up with it initially?

After training rats with cocaine as the only available reward, when exposed to saccharin they rapidly shifted their preference from cocaine to saccharin. (Lenoir et al 2007)

After a further experiment, giving rats only access to cocaine prior to the experiment, they still preferred saccharin.

Anxiogenic Effects

Rats may prefer saccharin over cocaine as a result of the anxiogenic effects exhibited when taking cocaine. However these effects only seem to have occurred near initial-cocaine taking - rats that later administrated cocaine did not exhibit much of these effects

Vulnerable Rats

Whilst the majority of rats preferred the sweetened water, there was a stable amount of rats (10% - 20% which preferred the cocaine).

They preferred cocaine over sucrose despite the fact that the sucrose would relieve them of their needed calories

  • Most rats learn to SA cocaine when no other choice is available
  • With extended access to cocaine, rats may develop changes that increasingly motivate them to take cocaine
  • However, attempts seem vain, as the majority of rats preferred the sweetened water regardless of attempts to "additise" them.