Lobeline does not serve as a reinforcer in rats.
BACKGROUND
Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats.


OBJECTIVE
The present experiments determined if lobeline serves as a reinforcer, if it decreases d-methamphetamine-induced reinstatement of d-methamphetamine self-administration, and if it activates the mesolimbic and nigrostriatal dopamine (DA) pathways in Sprague-Dawley male rats.


METHODS
The ability of intravenous (IV) lobeline (0.015-0.15 mg/kg per infusion) to engender responding and the ability of lobeline (0.015 and 0.05 mg/kg per infusion) to substitute for d-methamphetamine was determined using the self-administration paradigm. Experiments were also performed to determine if lobeline (1.0 and 3.0 mg/kg) reinstates responding for d-methamphetamine or alters the ability of d-methamphetamine (1.0 mg/kg per infusion) to reinstate responding following extinction. The effect of lobeline (3.0 mg/kg) or d-methamphetamine (1.0 and 3.0 mg/kg) on DA and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and striatum were also determined.


RESULTS
Lobeline was not self-administered and did not substitute for d-methamphetamine. Also, lobeline did not reinstate responding for d-methamphetamine following extinction nor did it alter d-methamphetamine-induced reinstatement. Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens or striatum.


CONCLUSIONS
Taken together, the present results indicate that lobeline decreases d-methamphetamine self-administration by decreasing reward, not by acting as a substitute reinforcer.
Harrod
Steven B
SB
Department of Psychology, University of Kentucky, 115 Kastle Hall, Lexington, KY 40506-0044, USA. sharr2@uky.edu
Dwoskin
Linda P
LP
Green
Thomas A
TA
Gehrke
Brenda J
BJ
Bardo
Michael T
MT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005108:Extinction, Psychological; D007262:Infusions, Intravenous; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
D018722:Nicotinic Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D008120:Lobeline; D004298:Dopamine