Which statement concerning the receptor subtypes involved in psychostimulant effects is true?
options: a) D2 receptors are required for cocaine self-administration. b) Pimozide, a D2 receptor blocker, completely eliminates amphetamine-induced euphoria. c) The locomotor-stimulating effects of cocaine involve the D5 receptor. d) D1 receptor knockout mice are insensitive to both the locomotor-stimulating and reinforcing effects of cocaine.
The correct answer and explanation is:
Correct Answer: d) D1 receptor knockout mice are insensitive to both the locomotor-stimulating and reinforcing effects of cocaine.
The D1 dopamine receptor plays a crucial role in mediating the behavioral effects of psychostimulant drugs like cocaine. Dopamine receptors are divided into two major families: D1-like (which includes D1 and D5 receptors) and D2-like (which includes D2, D3, and D4 receptors). The D1 receptor is heavily expressed in the striatum, a brain region critical for motor function and reward processing.
Experimental studies using genetically modified animals have shown that mice lacking D1 receptors (D1 receptor knockout mice) do not exhibit the typical increase in locomotor activity following administration of cocaine. Furthermore, these mice do not show the usual preference for environments associated with cocaine exposure, indicating a lack of reinforcement. This suggests that D1 receptor activation is necessary for both the locomotor stimulation and the rewarding effects that cocaine usually induces.
The other answer choices are incorrect for the following reasons:
- a) D2 receptors are required for cocaine self-administration: This is false. Although D2 receptors are involved in dopamine signaling, cocaine self-administration primarily depends on D1 receptor activity.
- b) Pimozide, a D2 receptor blocker, completely eliminates amphetamine-induced euphoria: This is false. While pimozide can reduce some effects of amphetamine, it does not completely eliminate the euphoric experience. Other receptor systems and pathways remain active.
- c) The locomotor-stimulating effects of cocaine involve the D5 receptor: This is also incorrect. Although D5 receptors are similar to D1 receptors, studies show that D1 receptors are more directly responsible for the behavioral effects of cocaine.
Thus, option d is the most accurate based on experimental evidence involving receptor function and psychostimulant behavior.