The basolateral complex of the amygdala mediates the modulation of intracranial self-stimulation threshold by drug-associated cues.
Learning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning- and memory-related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug-associated contextual cues on intracranial self-stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug-cue training sessions. Subsequent presentation of the drug-associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug-associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine-associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle.
Hayes
Robert J
RJ
Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Dr, Baltimore, Maryland 21224, USA. rhayes@intra.nida.nih.gov
Gardner
Eliot L
EL
D000679:Amygdala / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D012653:Self Stimulation / Q000502:physiology*
D009020:Morphine; D003042:Cocaine