Tolerance to amphetamine-induced inhibition of neuronal activity in the central amygdaloid nucleus

Rats were pretreated twice daily for 5 consecutive days with saline or 2.5 mg/kg d-amphetamine. Approximately 12 hr after the last injection, neuronal activity was recorded bilaterally from the central amygdaloid nucleus (CAN) and the animals were challenged every 2 min with 0.2 mg/kg d-amphetamine or with increasing incremental doses of apomorphine. In saline controls, all CAN neurons were inhibited by the 5th amphetamine injection and two-thirds were suppressed by 0.64 mg/kg apomorphine. In amphetamine-pretreated animals, on the other hand, the majority of CAN neurons failed to respond even by the 10th amphetamine injection and less than one-third were inhibited by apomorphine even at a dose of 2.56 mg/kg. These results indicate that tolerance develops to the inhibitory effects of d-amphetamine in the CAN and that this effect is mediated, at least in part, by a decrease in the sensitivity of postsynaptic dopamine receptors.