Faculty Collaboration Database

Prefrontal cortex D1 modulation of the reinforcing properties of cocaine. Brain Res 2006 Feb 23;1075(1):229-35

Date

02/08/2006

Pubmed ID

16460710

DOI

10.1016/j.brainres.2006.01.003

Scopus ID

2-s2.0-33644900267 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

The involvement of the dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) in the reinforcing properties of many drugs of abuse is well established. Though the prefrontal cortex (PFC) exhibits significant influence over activity in this pathway, its role in drug abuse is less defined. The present experiment investigated the impact of PFC D1 activity on cocaine self-administration (0.25, 0.75 mg/kg/inj) under progressive (PR) and fixed ratio (FR) schedules of reinforcement by assessing immediate and delayed effects of bilateral intra-PFC infusions of a D1 agonist (SKF 38393; 0.23 microg/side) and antagonist (SCH 23390; 0.25 microg/side). Immediately following infusion of dopaminergic agents or vehicle, no significant changes in self-administration occurred under any tested condition. However, 24 h after intra-PFC antagonist treatment, significantly lower PR breakpoints were observed for low (0.25 mg/kg), but not moderate (0.75 mg/kg) unit doses of self-administered cocaine. Locomotor activity levels during these assessments were unaffected by intra-PFC treatments. On an FR-3 schedule of reinforcement, the 0.25 cocaine unit dose elicited higher total cocaine intake and hyperlocomotor activation during a shorter session, but intra-PFC treatment had no significant effects on the number of reinforced responses or behavioral activity. The observation of decreased cocaine breakpoints after intra-PFC DA antagonist treatment reflects decrements in cocaine reinforcement efficacy. This finding corresponds temporally with previous work showing increased NAcc DA levels after similar treatment. Current findings demonstrate that transient changes in PFC DA neurotransmission can specifically influence reinforced behaviors without affecting overall behavioral activation.

Author List

Olsen CM, Duvauchelle CL

Author

Christopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Benzazepines
Cocaine
Conditioning, Operant
Dopamine Antagonists
Male
Prefrontal Cortex
Rats
Rats, Sprague-Dawley
Ventral Tegmental Area