Infusion of a D-1 receptor agonist into the nucleus accumbens enhances cocaine-induced behavioural sensitization.
The present study was designed to evaluate the effect of dopamine (DA) D-1 receptor activation in the nucleus accumbens (NAC) on the locomotor sensitizing effects of repeated intra-accumbens (intra-NAC) infusions of cocaine. Repeated infusion of cocaine (10 microg/0.5 microl daily for 2 days) resulted in an enhanced locomotor response to a subsequent intra-NAC and systemic (i.p.) challenging dose of the psychostimulant. Pretreatment with the selective D-1 agonist SK&F82958 (1.0 microg) markedly enhanced the sensitizing effects of both intra-NAC and systemic cocaine. The effect of SK&F82958 was completely blocked by systemic administration of the D-1 antagonist SCH23390 (0.1 mg/kg, i.p.). These data give further support to the idea that activation of D-1 receptors plays an important role in the induction of locomotor sensitization and show that the NAC may, in fact, be an anatomical locus of initiation of behavioural sensitization.
De Vries
T J
TJ
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Amsterdam, The Netherlands.
Cools
A R
AR
Shippenberg
T S
TS
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D007263:Infusions, Parenteral; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D014867:Water / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D014867:Water; C071262:SK&F 82958; D003042:Cocaine