Pharmacological Specificity of Delta 9-tetrahydrocannabinol Discrimination in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1995 Apr 1

PMID 7568628

Citations 27

Authors

R L Barrett

J L Wiley

R L Balster

B R Martin

Affiliations

Soon will be listed here.

Abstract

While many previous studies have shown that a variety of cannabinoids substitute and cross-substitute for delta 9-tetrahydrocannabinol (THC) in drug discrimination procedures, few have systematically examined potential THC-like effects of non-cannabinoid compounds. The purpose of the present study was to delineate further the pharmacological specificity of THC discrimination. Rats were trained to discriminate THC (3.0 mg/kg) from vehicle. Following determination of a dose-effect curve with THC, substitution tests with selected compounds from a variety of pharmacological classes, including l-phenylisopropyl adenosine, dizocilpine, dextromethorphan, clozapine, buspirone, MDL 72222, muscimol, midazolam and chlordiazepoxide, were performed. Whereas THC produced full dose-dependent substitution, substitution tests with non-cannabinoid drugs resulted in less than chance (50%) levels of responding on the THC-appropriate lever, with the exception of (+)-MDMA (2.5 mg/kg, 50%) and diazepam (3.0 mg/kg, 67%). These results are consistent with those of previous studies and suggest that the discriminative stimulus effects of THC exhibit pharmacological specificity.

Citing Articles

Enhancing translation: A need to leverage complex preclinical models of addictive drugs to accelerate substance use treatment options.

Corley C, Craig A, Sadek S, Marusich J, Chehimi S, White A Pharmacol Biochem Behav. 2024; 243():173836.

PMID: 39067531 PMC: 11344688. DOI: 10.1016/j.pbb.2024.173836.

Evaluation of cannabimimetic effects of selected minor cannabinoids and Terpenoids in mice.

Wiley J, Marusich J, Blough B, Namjoshi O, Brackeen M, Akinfiresoye L Prog Neuropsychopharmacol Biol Psychiatry. 2024; 132:110984.

PMID: 38417478 PMC: 11015967. DOI: 10.1016/j.pnpbp.2024.110984.

In vitro and in vivo pharmacological evaluation of the synthetic cannabinoid receptor agonist EG-018.

Gamage T, Barrus D, Kevin R, Finlay D, Lefever T, Patel P Pharmacol Biochem Behav. 2020; 193:172918.

PMID: 32247816 PMC: 7239729. DOI: 10.1016/j.pbb.2020.172918.

Evaluation of reinforcing and aversive effects of voluntary Δ-tetrahydrocannabinol ingestion in rats.

Barrus D, Lefever T, Wiley J Neuropharmacology. 2018; 137:133-140.

PMID: 29758385 PMC: 6278827. DOI: 10.1016/j.neuropharm.2018.04.018.

Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA.

Gamage T, Farquhar C, Lefever T, Marusich J, Kevin R, McGregor I J Pharmacol Exp Ther. 2018; 365(2):437-446.

PMID: 29549157 PMC: 5932312. DOI: 10.1124/jpet.117.246983.

References

Wiley J, Barrett R, Lowe J, Balster R, Martin B . Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats. Neuropharmacology. 1995; 34(6):669-76. DOI: 10.1016/0028-3908(95)00027-4. View

Pertwee R, Wickens A . Enhancement by chlordiazepoxide of catalepsy induced in rats by intravenous or intrapallidal injections of enantiomeric cannabinoids. Neuropharmacology. 1991; 30(3):237-44. DOI: 10.1016/0028-3908(91)90150-a. View

Compton D, GOLD L, Ward S, Balster R, Martin B . Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther. 1992; 263(3):1118-26. View

GOLD L, Balster R, Barrett R, Britt D, Martin B . A comparison of the discriminative stimulus properties of delta 9-tetrahydrocannabinol and CP 55,940 in rats and rhesus monkeys. J Pharmacol Exp Ther. 1992; 262(2):479-86. View

Kelly T, Foltin R, Emurian C, FISCHMAN M . Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam. J Anal Toxicol. 1993; 17(5):264-72. DOI: 10.1093/jat/17.5.264. View

Pertwee R, Greentree S . Delta-9-tetrahydrocannabinol-induced catalepsy in mice is enhanced by pretreatment with flurazepam or chlordiazepoxide. Neuropharmacology. 1988; 27(5):485-91. DOI: 10.1016/0028-3908(88)90130-x. View

Pertwee R, Greentree S, Swift P . Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice. Neuropharmacology. 1988; 27(12):1265-70. DOI: 10.1016/0028-3908(88)90029-9. View

Onaivi E, Green M, Martin B . Pharmacological characterization of cannabinoids in the elevated plus maze. J Pharmacol Exp Ther. 1990; 253(3):1002-9. View

Mokler D, Nelson B, Harris L, ROSECRANS J . The role of benzodiazepine receptors in the discriminative stimulus properties of delta-9-tetrahydrocannabinol. Life Sci. 1986; 38(17):1581-9. DOI: 10.1016/0024-3205(86)90497-2. View

10.

Sethi B, Trivedi J, Kumar P, Gulati A, Agarwal A, Sethi N . Antianxiety effect of cannabis: involvement of central benzodiazepine receptors. Biol Psychiatry. 1986; 21(1):3-10. DOI: 10.1016/0006-3223(86)90003-x. View

11.

Jarbe T, McMillan D . Discriminative stimulus properties of tetrahydrocannabinols and related drugs in rats and pigeons. Neuropharmacology. 1979; 18(12):1023-4. DOI: 10.1016/0028-3908(79)90171-0. View

12.

Browne R, Weissman A . Discriminative stimulus properties of delta 9-tetrahydrocannabinol: mechanistic studies. J Clin Pharmacol. 1981; 21(S1):227S-234S. DOI: 10.1002/j.1552-4604.1981.tb02599.x. View

13.

Pertwee R . The central neuropharmacology of psychotropic cannabinoids. Pharmacol Ther. 1988; 36(2-3):189-261. DOI: 10.1016/0163-7258(88)90106-4. View

14.

Jarbe T, Hiltunen A . Limited stimulus generalization between delta 9-THC and diazepam in pigeons and gerbils. Psychopharmacology (Berl). 1988; 94(3):328-31. DOI: 10.1007/BF00174684. View

15.

Balster R, Prescott W . Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication. Neurosci Biobehav Rev. 1992; 16(1):55-62. DOI: 10.1016/s0149-7634(05)80051-x. View

16.

Jarbe T, Hiltunen A . Cannabimimetic activity of cannabinol in rats and pigeons. Neuropharmacology. 1987; 26(2-3):219-28. DOI: 10.1016/0028-3908(87)90212-7. View

17.

Wiley J, Barrett R, Britt D, Balster R, Martin B . Discriminative stimulus effects of delta 9-tetrahydrocannabinol and delta 9-11-tetrahydrocannabinol in rats and rhesus monkeys. Neuropharmacology. 1993; 32(4):359-65. DOI: 10.1016/0028-3908(93)90157-x. View

18.

Sung S, JAKUBOVIC A . Interaction of a water-soluble derivative of delta-9-tetrahydrocannabinol with [3H]diazepam and [3H]flunitrazepam binding to rat brain membranes. Prog Neuropsychopharmacol Biol Psychiatry. 1987; 11(2-3):335-40. DOI: 10.1016/0278-5846(87)90078-9. View

19.

Hollister L, GILLESPIE H . The benzodiazepine receptor antagonist, flumazenil does not block clinical effects of delta-9-tetrahydrocannabinol. Life Sci. 1990; 47(18):1655-60. DOI: 10.1016/0024-3205(90)90371-w. View