Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats.
BACKGROUND
Chronic opiate administration induces neuroadaptations within the nucleus accumbens (NAc) and ventral tegmental area (VTA) that can contribute to dependence. We have shown that morphine dependence shifts the behavioral consequences of D1 dopamine (DA) receptor signaling: systemic administration of a D1 receptor agonist is rewarding and blocks naloxone-precipitated withdrawal signs in morphine-dependent rats, but has minimal effects in nondependent rats. These data suggest that D1 receptors acquire the ability to regulate reward and withdrawal in morphine-dependent rats. The brain regions involved in these effects are not known.


OBJECTIVE
Studies were designed to test the hypothesis that the nucleus accumbens shell (NASh) and the ventral tegmental area (VTA) are important sites for mediating the behavioral effects of D1 receptor activation in morphine-dependent rats.


METHODS
The effects of microinjecting the D1 receptor agonist SKF 82958 into the NASh or the VTA on place conditioning and somatic withdrawal signs were studied in morphine-dependent and nondependent rats.


RESULTS
Intra-NASh microinjection of SKF 82958 (1 microg/side) established conditioned place preferences in morphine-dependent but not nondependent rats, but had no effect on naloxone-induced place aversions or somatic withdrawal signs. Intra-VTA microinjection of SKF 82958 (2 microg) did not establish place preferences under any conditions, but blocked naloxone-induced place aversions without effects on somatic withdrawal signs.


CONCLUSIONS
There is an anatomical dissociation between D1 receptor-mediated reward and relief of withdrawal in morphine-dependent rats. When combined, the individual effects of D1 receptor activation in the NASh and VTA on the affective signs of precipitated morphine withdrawal resemble those seen with systemic administration.
Chartoff
Elena H
EH
Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 218, 115 Mill Street, Belmont, MA 02478, USA. echartoff@mclean.harvard.edu
Barhight
Matthew F
MF
Mague
Steve D
SD
Sawyer
Allison M
AM
Carlezon
William A
WA
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009021:Morphine Dependence / Q000523:psychology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000523:psychology*; D017557:Ventral Tegmental Area / Q000502:physiology
D001552:Benzazepines; D018491:Dopamine Agonists; D009292:Narcotic Antagonists; D017447:Receptors, Dopamine D1; D009270:Naloxone; C067113:SK&F 81297; C071262:SK&F 82958