Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats.
BACKGROUND
Orbital/insular areas of the prefrontal cortex (PFC) are implicated in cocaine addiction. However, the role of dopamine D1 receptors in mediating cocaine self-administration in these sub-regions remains unknown.


OBJECTIVE
To define the role of the dorsal agranular insular (AId) sub-region of the PFC, we investigated the effects of D1 receptor manipulation on self-administration behavior maintained by cocaine and cocaine-related stimuli.


METHODS
Rats were trained to lever press for cocaine (1 mg/kg) under a fixed-interval 5-min (fixed-ratio 5:S) second-order schedule of reinforcement in the presence of conditioned light cues and contextual sound cues. Intra-AId infusions of vehicle, the D1-like receptor agonist SKF 81297 (0.1, 0.2, 0.4 microg/side) or the D1-like receptor antagonist SCH 23390 (1.0, 2.0, 4.0 microg/side), were administered prior to 1-h self-administration test sessions. Food-maintained responding under a second-order schedule was examined in separate rats to determine if pretreatment with D1 ligands produced general impairments in responding.


RESULTS
Infusion of SKF 81297 (0.2 and 0.4 microg/side) reduced active lever responses during the first 30 min of 1-h test sessions, but did not influence cocaine intake. Infusion of 4.0 microg/side SCH 23390 reduced active lever responses and cocaine intake throughout the 1-h test sessions. Additionally, this dose of SCH 23390 disrupted food-maintained responding and intake.


CONCLUSIONS
D1 receptor agonists and antagonists in the AId have diverse consequences and time courses of action. D1 receptor stimulation in the AId may reduce the motivating influence of cocaine-related stimuli on responding whereas D1 receptor blockade in this PFC sub-region produces global disruptions in behavior.
Di Pietro
Nina C
NC
Laboratory of Behavioral Neuroscience, Department of Psychology and Program in Neuroscience, Boston University, 64 Cummington St., Boston, MA 02215, USA.
Mashhoon
Yasmin
Y
Heaney
Chelcie
C
Yager
Lindsay M
LM
Kantak
Kathleen M
KM
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; C067113:SK&F 81297