Interactions between 18-methoxycoronaridine (18-MC) and cocaine: dissociation of behavioural and neurochemical sensitization.
The phenomenon of sensitization has been implicated in various aspects of drug addiction. As such, the present study determined the effects of a potential anti-addictive agent, 18-methoxycoronaridine (18-MC; 40 mg/kg, IP, 19 h earlier), on the expression of sensitization following the repeated administration of cocaine (COC; five once daily injections of 15 mg/kg, IP) or saline. The effects of 18-MC on COC metabolism were also assessed. Compared to vehicle controls, 18-MC significantly enhanced the expression of COC-induced locomotion (0, 10, 20 and 40 mg/kg, IP) in chronic COC treated rats only. In both acute and chronic COC rats, 18-MC potentiated the stereotypy induced by higher COC doses (20 and 40 mg/kg, IP). In contrast, 18-MC abolished the sensitized dopamine (DA) response in the nucleus accumbens (NAC) to COC (20 mg/kg), without altering the DA response of acute COC rats. None of the interactions between 18-MC and COC appear to be related to alterations in COC metabolism as no effect of 18-MC pretreatment was observed on extracellular levels of COC or two of its metabolites, benzoylecogonine and norcocaine. From the present findings, it is concluded that the enhancement of COC-induced behaviour produced by 18-MC pretreatment is independent of effects on either COC pharmacokinetics or COC-induced alterations in DA transmission. However, given that 18-MC decreases the self-administration of COC in laboratory animals, it is proposed that the anti-addictive efficacy of 18-MC might be related to an ability to selectively block the expression of sensitized extracellular levels of DA in the NAC in rats with previous COC experience.
Szumlinski
K K
KK
Center for Neuropharmacology and Neuroscience (MC-136), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. szumlik@mail.amc.edu
McCafferty
C A
CA
Maisonneuve
I M
IM
Glick
S D
SD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000493:pharmacokinetics*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology*; D005260:Female; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D007050:Ibogaine; D003042:Cocaine; C103345:18-methoxycoronaridine; D004298:Dopamine