**Core Concept**
The concept of substance dependence involves the complex interplay of various physiological, psychological, and behavioral adaptations that occur in response to repeated exposure to a substance. The development of dependence is characterized by a range of changes in brain function and structure, including alterations in neurotransmitter systems and synaptic plasticity.

**Why the Correct Answer is Right**
During the early stages of substance dependence, the brain undergoes significant changes, including the development of tolerance and withdrawal symptoms. Tolerance occurs when the brain adapts to the presence of the substance by reducing the sensitivity of its receptors, leading to the need for increasingly higher doses to achieve the same effect. Withdrawal symptoms, on the other hand, occur when the substance is suddenly removed or its concentration is decreased, leading to an imbalance in neurotransmitter systems. The development of tolerance and withdrawal symptoms is a hallmark of substance dependence and is thought to be mediated by changes in the function of the brain's reward system, including the release of dopamine and other neurotransmitters.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it does not accurately describe the early stages of substance dependence.
**Option B:** This option is incorrect because it is a symptom of advanced substance dependence, not an early sign.
**Option C:** This option is incorrect because it is a characteristic of substance use disorder in general, not a specific early sign of dependence.

**Clinical Pearl / High-Yield Fact**
One key aspect of substance dependence is the concept of "kindling," where repeated exposure to a substance leads to an increase in the severity and duration of withdrawal symptoms.

**Correct Answer: C. Tolerance.**