Two discrete nucleus accumbens projection areas differentially mediate cocaine self-administration in the rat.
The region of the nucleus accumbens and its connections have been implicated in the reinforcing actions of cocaine as measured by intravenous self-administration. Our previous work has demonstrated that ibotenic acid lesions of one of the output regions of the nucleus accumbens, the sublenticular region of the extended amygdala (SEA), resulted in significant decreases in the highest ratio obtained in rats self-administering cocaine. In the present study, the importance of another nucleus accumbens output, the subcommissural ventral pallidum (SVP), in mediating the self-administration of cocaine in the rat was explored. Animals were trained to self administer cocaine (0.75 mg/kg/inj) via an intravenous catheter on a FR5 schedule of reinforcement. Subsequently, subjects were either given bilateral intracerebral injections (0.5 microliter per side) of ibotenic acid (10 micrograms/microliter lesion group) or vehicle (sham group) into the SVP or into the SEA. Four days postlesion, cocaine self-administration on a FR5 schedule was resumed for 3 days. Next, a dose effect function was determined in one 3-h session. Finally, a progressive ratio probe in which the ratio requirement was increased after each reinforcement was tested. Lesions of both the SVP and the SEA produced significant changes in responding for intravenous cocaine on a FR5 schedule of reinforcement as compared to sham lesioned controls, although the effect was found to be greater for the rats bearing lesions of the SEA. While the lesions produced decreases in responding for cocaine at all doses tested in the dose-effect function, the rate of responding was still inversely proportional to the dose in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Robledo
P
P
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Koob
G F
GF
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D007051:Ibotenic Acid; D003042:Cocaine; D004298:Dopamine