Cellular responses of nucleus accumbens neurons to opiate-seeking behavior: I. Sustained responding during heroin self-administration.
The nucleus accumbens (NAcc) has been hypothesized to be a critical component of the circuit mediating opiate-seeking behaviors. To further explore the electrophysiological correlates of opiate-seeking behavior, we recorded neurons in the NAcc and in the medial prefrontal cortex (mPFC) of rats trained to self-administer heroin for at least 2 weeks. Rats were trained to lever press (FR-1 schedule) for an intravenous (i.v.) infusion of heroin (0.06 mg/kg/injection) in an operant chamber. Spontaneous single unit activity in the NAcc and the mPFC was then recorded while animals were allowed to self-administer heroin. Our data suggest that about 20% (8/42) of the NAcc neurons studied exhibited an inhibitory response immediately after heroin self-administration. However, most of the NAcc neurons studied (76%; 32/42) were not affected during heroin self-administration. In contrast, noncontingent injection of a similar dose of heroin (0.06 mg/kg/injection) had no effect on NAcc spontaneous activity (0/6). On the other hand, passive administration of higher doses of heroin (0.2-0.6/mg/kg/injection) markedly suppressed the firing rate in 46% (6/13) of the neurons studied. These effects of heroin on NAcc activity were antagonized by systemic administration ofnaloxone (4-6 mg/kg, i.v.). Studies characterizing the responses of mPFC neurons during heroin self-administration showed that 40% (2/5) of the neurons tested exhibited an inhibitory effect immediately after heroin self-administration. These data suggest that in animals well-trained to self-administer heroin, only a small number (20%) of the NAcc neurons studied responded to heroin self-administration. Further research is necessary to determine whether these responses are a function of the opiate-seeking state of the animal and the mechanism(s) responsible for these effects of heroin.
Lee
R S
RS
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Criado
J R
JR
Koob
G F
GF
Henriksen
S J
SJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D003932:Heroin / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000523:psychology
D009294:Narcotics; D003932:Heroin