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.
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Amsterdam, The Netherlands.
T J
TJ
De Vries
A R
AR
Cools
T S
TS
Shippenberg
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