People who have an extensive history of cocaine use, often report that the pleasure that they receive by utilizing the drug gradually decreases, even though their addictive behavior towards the drug, gradually intensifies. A recent study that documented the effects that cocaine had on the neurons in the reward system of mice shed some light as to why this may be the case for cocaine users and other illicit drug abusers as well.
The study demonstrated that there was a cocaine-induced imbalance, in a portion of the mice’s brain that’s associated with the reward system. The researchers argue that as far as humans go, this could explain the reasons why long-time cocaine users may experience a weaker high, yet stronger compulsion to acquire the drug, after prolonged use.
During the study, the research team divided the mice into two groups. The first group was given cocaine on a daily basis for two weeks. The second group was exposed to cocaine for the first time. By utilizing an imaging and measurement technique, they were able to measure the drug’s impact on the activity levels of two populations of medium spiny neuron within the mice’s brain. One of the observations that the research team noticed was that whenever one of the two populations of medium spiny neuron interacted with dopamine, (D1R), it increased the level of euphoria the animals were feeling which subsequently motivated the animal to repeat the experience in order for them to receive the same feelings. The other population of medium spiny neurons interacts with dopamine through a different receptor by the name of D2R. Whenever this receptor was activated after the mice was injected with cocaine, it caused an attenuation or reduction in euphoria and drug-seeking activity.
What’s so interesting about this activity is that during the experiment they found that D1R activation increased and D2R activation decreased immediately after the mice were injected with cocaine. However, in both groups, the ratio of D1R activation and D2R activation, shifted in favor of the reward and motivation promoting effects of D1R. Meaning that, even though both groups of mice experienced the counter effects of D2R when it was activated, which causes a reduction of euphoria and drug seeking tendencies, there was a higher level of activation within the D1R receptors. The researchers argue that this demonstrates why people continue to seek drugs, despite the fact that the effects they experience gradually diminishes after prolonged use while their cravings gradually increase.
Additionally, Dr. Pan explained that dopamine has the ability to activate and inhibit brain circuits as well. He says that this dual action actually produces positive, healthy behavioral outcomes. However, cocaine usage upsets this “dual action balance.” It essentially, enhances the effects that activation of the D1R receptors causes which promotes drug seeking behaviors in both in animals and humans and suppresses the D2R receptors that would usually cause the individual to refrain from conducting such behaviors. The research team also proclaimed that this demonstrated that the imbalance that the mice who utilized the drug for the first time experienced were short lived. But, the effects that this imbalance caused in the mice that were continuously exposed to the drug lasted for a much longer period of time.