Mutant mice with no DA transporters _

Mutant mice with no DA transporters _ ?

A die a few weeks after birth

B do not respond to hallucinogens.

C do not respond to psychostimulants — cocaine and amphetamine.

D have an increased sensitivity to psychostimulants

The correct answer and explanation is:

The correct answer is:

C. do not respond to psychostimulants — cocaine and amphetamine.

Explanation:

Dopamine (DA) transporters (DAT) play a crucial role in regulating dopamine levels in the brain by reuptaking dopamine from the synaptic cleft back into presynaptic neurons. This process controls dopamine signaling, which is vital for normal brain function, particularly in the reward, motor, and cognitive systems.

Mutant mice lacking dopamine transporters (DAT knockout mice) have been extensively studied to understand the role of dopamine in behavior and drug response. Here’s why option C is correct:

1. Role of DAT in Psychostimulant Action:
   Psychostimulants like cocaine and amphetamine exert their effects primarily by targeting DAT. Cocaine blocks DAT, preventing dopamine reuptake, which leads to an increase in extracellular dopamine levels and heightened dopaminergic signaling. Amphetamine, on the other hand, enters the neuron via DAT and promotes dopamine release into the synapse, also increasing dopamine signaling.
2. Lack of DAT Abolishes Psychostimulant Effect:
   In DAT knockout mice, since there are no dopamine transporters, cocaine has no transporter to block, and amphetamine cannot enter the neurons to cause dopamine release. Therefore, these mice do not show the usual behavioral or biochemical responses to these psychostimulants, effectively making them “non-responsive.”
3. Behavioral and Physiological Effects:
   DAT knockout mice show elevated baseline dopamine levels because dopamine is not reabsorbed efficiently. Despite this, the absence of DAT disrupts the normal dopamine dynamics required for psychostimulant drugs to have an effect. These mice tend to be hyperactive due to elevated dopamine but do not increase activity further upon administration of cocaine or amphetamine.

Why Other Options Are Incorrect:

• A. die a few weeks after birth: DAT knockout mice survive beyond birth and live into adulthood, although they may have some physiological abnormalities, they do not die within weeks after birth.
• B. do not respond to hallucinogens: Hallucinogens primarily affect serotonin receptors (e.g., 5-HT2A), not dopamine transporters. So DAT absence does not eliminate response to hallucinogens.
• D. have an increased sensitivity to psychostimulants: Actually, they have decreased or no sensitivity because the drugs act through DAT.

Summary

Mutant mice lacking dopamine transporters cannot respond to cocaine or amphetamine because these drugs need DAT to exert their effects. This makes option C the correct answer.