Intra-accumbens pertussis toxin sensitizes rats to the locomotor activating effects of a single cocaine challenge.
Drugs of abuse share common neurochemical signaling substrates, many of which are components of the cAMP cascade. Interestingly, a number of these substrates have been linked to drug-influenced behaviors. This study sought to understand the role of one signaling substrate, inhibitory G-proteins, in a drug-induced phenomenon known as behavioral sensitization. Specifically, we used pertussis toxin (PTX) as a tool to investigate the relationship between cocaine-induced alterations in cAMP signaling and behavior. Vehicle (1 micro l/side) or PTX (0.15 or 0.25 micro g/1 micro l/side) was bilaterally infused into the nucleus accumbens of rats. Locomotor activity was assessed on days 7, 14 and 21 post-infusion. Intra-accumbal PTX produced a dose-dependent increase in locomotor activity. On day 21 following behavioral monitoring for 1 h, rats were acutely challenged with cocaine (15 mg/kg, i.p.) and behavioral data were accumulated for an additional 2 h. Intra-accumbal PTX sensitized rats to the locomotor-activating effects of a single cocaine challenge which was dose-dependent. After behavioral testing, brains were removed and processed for in vitro receptor autoradiography using the D(1) receptor ligand [3H] SCH 23390. No changes in D(1) dopamine receptor binding were observed. These findings suggest a role for inhibitory proteins (G(i)/G(o)) within the nucleus acumbens in locomotor activity and also cocaine-induced behavioral sensitization.
Hummel
Michele
M
Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street MRB 321, Philadelphia, PA 19140, USA. michele_hummel@msn.com
Unterwald
Ellen M
EM
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D017447:Receptors, Dopamine D1 / Q000378:metabolism
D017447:Receptors, Dopamine D1; D037342:Pertussis Toxin; D003042:Cocaine