Opioid receptors in the basolateral amygdala but not dorsal hippocampus mediate context-induced alcohol seeking

Abstract

Contexts associated with the availability of alcohol can induce craving in humans and alcohol seeking in rats. The opioid antagonist naltrexone attenuates context-induced reinstatement (renewal) of alcohol seeking and suppresses neuronal activation in the basolateral amygdaloid complex and dorsal hippocampus induced by such reinstatement. The objective of this study was to determine whether pharmacological blockade of opioid receptors in the basolateral amygdala or dorsal hippocampus would attenuate the context-induced reinstatement of alcohol seeking. Rats were trained to self-administer alcohol in one context (Context A), extinguished in a distinct context (Context B) and then tested for reinstatement of alcohol seeking in A and B contexts. Prior to the test session, rats were bilaterally microinjected with 0, 333 or 1000ng (total) naloxone methiodide into the basolateral amygdala or dorsal hippocampus. Naloxone methiodide in the amygdala, but not the hippocampus, dose dependently suppressed context-induced reinstatement. This suggests that opioid transmission in the basolateral amygdaloid complex is an important mediator of context-induced alcohol seeking.

Figure 1

(A) A representative photomicrograph of the injection site (A) and illustrations of bilateral injection sites for all the animals (B) with intra-amygdala infusions. Active (C) and inactive (D) lever presses on the reinstatement test days in the extinction (ABB) and self-administration (ABA) contexts following bilateral intra-amygdala infusions of 0, 333 and 1000 ng total naloxone methiodide (NLX-MI) per rat. *denotes a significant difference from the ABB condition (p < 0.05), †denotes a significant difference from the vehicle treated group in the ABA condition (p < 0.05).

Figure 2

(A) A representative photomicrograph of the injection site (A) and illustrations of bilateral injection sites for all the animals (B) with intra-hippocampal infusions. Active (C) and inactive (D) lever presses on the reinstatement test days in the extinction (ABB) and self-administration (ABA) contexts following bilateral intra-dorsal hippocampus infusions of 0, 333 and 1000 ng total naloxone methiodide (NLX-MI) per rat. *denotes a significant difference from the ABB condition (p < 0.05).