Characterization of [3H]cytisine binding to human brain membrane preparations

Hall, Margot; Zerbe, L.; Leonard, Scott F.; Freedman, Robert B.

doi:10.1016/0006-8993(93)90410-o

Cited by 63 publications

(28 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ligandbinding studies, tritiated nicotine and cytisine mark an almost identical population of putative nicotinic receptors, and cytisine has a substantially higher affinity than nicotine at this site (Pabreza et al 1991;Hall et al 1993). The anatomical distributions of cytisine and nicotine binding are very similar in rat and human brain (Pabreza et al 1991;Rubboli et al 1994).…”

Section: Discussionmentioning

confidence: 95%

“…Interest in cytisine has been increasing due to the use of [3H]-cytisine in ligand-binding studies, where it seems to mark a population of receptors that are almost if not completely identical to those labelled by [3H]-nicotine (Pabreza et al 1991;Hall et al 1993;Anderson and Arneric 1994;Rubboli et al 1994). In studies where nicotinic agonists have been examined on preparations ofXenopus oocytes expressing defined subtypes of nicotinic receptor, cytisine has been found to have complex agonist and antagonist effects that depend upon the particular subtype of receptor present (Luetje and Patrick 1991;Covernton et al 1994;Papke and Heinemann 1994).…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Discriminative stimulus properties of the nicotinic agonist cytisine

Chandler

Stolerman

1997

Psychopharmacology

View full text Add to dashboard Cite

Cytisine binds with high affinity and specificity to neuronal nicotinic receptors but its physiological and behavioural effects are complex and differ from those of nicotine. The present study explores the behavioural aspects further by comparing the discriminative stimulus effects of cystisine with those of nicotine. Two groups of rats were trained to discriminate cytisine (2 mg/kg s.c.) or nicotine (0.2 mg/kg s.c.) from saline in a two-lever operant conditioning procedure with food reinforcers presented on a tandem VI FR schedule. A third group of rats was trained to discriminate cytisine (3 mg/kg s.c.). Rats acquired these discriminations within 50 training sessions. The stimulus effects of both cytisine and nicotine appeared within 4 min of s.c. injection. In generalization tests, rats trained with either cytisine or nicotine showed steep dose-response curves (generalization gradients) for their respective training drug. However, rats trained with cytisine showed full dose-related, generalization to nicotine (93%), whereas rats trained with nicotine exhibited only partial generalization to cytisine (54%). Rats trained with either cytisine or nicotine exhibited similar, partial generalization (76-77%) to (+)-amphetamine. The nicotine antagonist mecamylamine blocked the discriminative stimulus effects of both cytisine and nicotine; it was confirmed that the block of nicotine (0.2 mg/kg) was complete, whereas the block of cytisine (2 and 3 mg/kg) was incomplete in two separate experiments. Overall, the results showed that cytisine, like nicotine, can serve as a robust discriminative stimulus but, in contrast to its relatively high affinity in binding experiments, cytisine was much less potent than nicotine in the behavioural studies. Although the stimulus effects of the two drugs were very similar, there were some subtle differences such as the asymmetrical cross-generalizations between them and possible small differences in susceptibility to antagonism by mecamylamine. These effects were interpreted either in terms of a putative partial agonist effect of cytisine, or by assuming that nicotine produces a compound stimulus. Such a stimulus would be mediated through two or more subtypes of nicotinic receptor, and cytisine would act at some, but not all, of these receptor subtypes.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

Discriminative stimulus properties of the nicotinic agonist cytisine

Chandler

Stolerman

1997

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…As above, we first determined the concentration or dilution of plant extract required to block 50% of the specific bound [3H]epibatidine in rat brain homogenates. We then tested this concentration against [3H]cytisine, which, like nicotine, preferentially binds a4/h2 nicAChRs (Hall et al, 1993;Zhang and Steinbach, 2003), and then against [3H]Methyllycaconitine which is selective for the a7 nicAChR subtype (Davies et al, 1999) for which nicotine has very little affinity, (Yum et al, 1996). We then calculated the DDR for each standard compound or extract.…”

Section: Introductionmentioning

confidence: 99%

Novel approaches to plant drug discovery based on high throughput pharmacological screening and genetic manipulation

2005

View full text Add to dashboard Cite

“…The final pellet was resuspended in 25 ml of fresh buffer, and triplicate aliquots of homogenate equivalent to approximately 1.2 mg of protein were added to test tubes containing 5 nM eH)cytisine. We used cytisine because it has high affinity for the receptor, and unlike nicotine, exhibits a low nonspecific binding component (16). After adding buffer to a final volume of I ml, memo branes were incubated for 75 min at room temperature in the presence and absence of 100 nM or 1000 oM unlabeled nicotine, cotinine, cocaine, dopamine, carbachol, and D-tubocurarine.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Cotinine on Nicotine- and Cocaine-Induced Dopamine Release in the Nucleus Accumbens

et al. 1999

View full text Add to dashboard Cite

Cotinine is the major metabolite of nicotine. Nicotine is rapidly metabolized and has a short half-life, but cotinine is metabolized and eliminated at a much lower rate. Because of the resulting increase with time in the cotinine to nicotine ratio in the body, including in the brain, it is of interest to examine the effect of cotinine on nicotine-induced changes. In studies on conscious, freely-moving rats, intravenous administration of either nicotine or cocaine induced the release of dopamine in the nucleus accumbens, as assayed by microdialysis. Prior intravenous administration of a high dose of cotinine (500 microg/kg) inhibited this nicotine- or cocaine-induced dopamine release. The action of cotinine does not seem to occur through its effect on the metabolism of nicotine or on its binding at the receptor site, because cotinine, unlike nicotine, does not affect the binding of the nicotinic ligand cytisine. The findings suggest that cotinine affects a putative component of the reward mechanism, and as such could have therapeutic value.

show abstract

Characterization of [3H]cytisine binding to human brain membrane preparations

Cited by 63 publications

References 16 publications

Discriminative stimulus properties of the nicotinic agonist cytisine

Discriminative stimulus properties of the nicotinic agonist cytisine

Novel approaches to plant drug discovery based on high throughput pharmacological screening and genetic manipulation

The Effect of Cotinine on Nicotine- and Cocaine-Induced Dopamine Release in the Nucleus Accumbens

Contact Info

Product

Resources

About