Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys

@article{Kimmel2007FasterOA,
  title={Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys},
  author={Heather L. Kimmel and Joann A O'connor and F. Ivy Carroll and Leonard Lee Howell},
  journal={Pharmacology Biochemistry and Behavior},
  year={2007},
  volume={86},
  pages={45-54}
}
View on Elsevier
europepmc.org
50 Citations
Highly Influential Citations
1
Background Citations
25
Methods Citations
12
Results Citations
2

Figures and Tables from this paper

50 Citations

Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys
Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI-177 compared to cocaine in nonhuman primates
Effects of Serotonin 2C Receptor Agonists on the Behavioral and Neurochemical Effects of Cocaine in Squirrel Monkeys
TLDR
The results suggest that 5-HT2CR agonists functionally antagonize the behavioral effects of cocaine in nonhuman primates, possibly via a selective modulation of cocaine-induced dopamine increases within the mesolimbic dopamine system and may therefore represent a novel class of pharmacotherapeutics for the treatment of cocaine abuse.
Behavioral and neurochemical effects of amphetamine analogs that release monoamines in the squirrel monkey
Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep, and hormone levels in rhesus monkeys.
TLDR
Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures.
Simultaneous measurement of extracellular dopamine and dopamine transporter occupancy by cocaine analogs in squirrel monkeys
TLDR
The results suggest a lack of concordance between drug occupancy at DAT and changes in DA levels, and indicate that acute cocaine administration decreases the availability of plasma membrane DAT for binding, even after cocaine is no longer blocking DA uptake as evidence by a return to basal DA levels.
Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys
TLDR
Overall, the reported behavioral effects of DBH inhibition in rodent models of relapse did not extend to nonhuman primates under the conditions used in the current studies.
Effects of Histamine H3 Receptor Activation on the Behavioral-Stimulant Effects of Methamphetamine and Cocaine in Mice and Squirrel Monkeys
TLDR
A role of H3R is suggested in the behavioral-stimulant effects of METH, but not cocaine, in mice and monkeys, and no role in monkeys.
The Serotonin 2C Receptor Antagonist SB 242084 Exhibits Abuse-Related Effects Typical of Stimulants in Squirrel Monkeys
TLDR
These studies are the first to assess the direct reinforcing effects of a 5-HT2CR-selective antagonist in any species and suggest that SB 242084 exhibits a behavioral profile that is qualitatively similar to other psychostimulants, although its efficacy is modest compared with cocaine.
Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors
TLDR
Low abuse liability of BZT analogs is supported and their potential development as medications for cocaine abuse is supported by the effects of their oral pretreatment on cocaine self-administration.
...
...

References

SHOWING 1-10 OF 61 REFERENCES
Characterization of the effects of cocaine and GBR 12909, a dopamine uptake inhibitor, on behavior in the squirrel monkey.
  • L. Howell, L. D. Byrd
  • Biology, Psychology
    The Journal of pharmacology and experimental therapeutics
  • 1991
The behavioral effects of cocaine and GBR 12909, a highly selective dopamine uptake inhibitor, were compared in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus…
Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey.
TLDR
The results indicate that the behavioral pharmacology of RTI-113 is similar to that of cocaine, further implicating a prominent role for dopamine uptake inhibition in the behavioral effects of cocaine.
Serotonergic modulation of the behavioral effects of cocaine in the squirrel monkey.
  • L. Howell, L. D. Byrd
  • Biology, Psychology
    The Journal of pharmacology and experimental therapeutics
  • 1995
TLDR
The pharmacological profile of effects of selective 5 HT uptake inhibitors and direct agonists indicates that the behavioral-stimulant and reinforcing effects of cocaine do not depend on inhibition of 5HT uptake, whereas the drug interactions suggest that the serotonergic system can modulate specific behavioral effects of Cocaine.
Effects of Dopamine Transporter Inhibitors on Cocaine Self-Administration in Rhesus Monkeys: Relationship to Transporter Occupancy Determined by Positron Emission Tomography Neuroimaging
TLDR
The results indicate that selective DAT inhibitors may require high DAT occupancy to reduce cocaine self-administration and maintain drug self-Administration, and the behavioral profile of DAT inhibitor may be influenced by actions at other monoamine transporters.
Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse
TLDR
The discovery and preclinical development of selective dopamine reuptake inhibitors as potential pharmacotherapies for treating cocaine addiction are presented and 3β-(4-chlorophenyl)-2β-[3-(4'-methylphenyl)isoxazol-5-yl]tropane (RTI-336) has been selected forPreclinical development.
Serotonergic attenuation of the reinforcing and neurochemical effects of cocaine in squirrel monkeys.
TLDR
The results obtained suggest that increasing brain 5-HT activity can attenuate the reinforcing effects of cocaine, ostensibly by decreasing the ability of cocaine to elevate extracellular DA in brain areas that mediate the behavioral effects.
In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys
TLDR
Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques, and further support a role for the DAT in the abuse liability of local anesthetics.
Reinforcing Strength of a Novel Dopamine Transporter Ligand: Pharmacodynamic and Pharmacokinetic Mechanisms
TLDR
The results suggest that (+)-CPCA is a weaker positive reinforcer than cocaine because it has a slower onset of action over the first few minutes after i.v. injection.
The Reinforcing Efficacy of Psychostimulants in Rhesus Monkeys: The Role of Pharmacokinetics and Pharmacodynamics
TLDR
There was not a linear relationship between monoamine transporter affinity and reinforcing efficacy, but it appeared that in nonhuman primates there is a range of DAT affinity under which maximal responding is maintained, and the 5-HTT-selective cocaine analog HD-60 functioned robustly as a reinforcer at several doses in all monkeys tested.
Locomotor stimulant effects of novel phenyltropanes in the mouse.
...
...