Skip to main content
SpringerLink
Log in

Drug Discrimination Studies for Investigations on the Mechanisms of Action of GABAB Receptor Ligands

  • Chapter
  • First Online:
GABAB Receptor

Part of the book series: The Receptors ((REC,volume 29))

  • 825 Accesses

Abstract

Drug discrimination is a reliable, sensitive, and pharmacologically specific behavioral procedure for studying the mechanism of action of drugs. These qualities have enabled investigators to classify and differentiate closely related compounds and gather important information concerning their mechanism(s) of action in vivo. Although drugs from various pharmacological classes have been used to establish discriminative stimulus control, the focus of this chapter is on how drug discrimination procedures have been used to study the in vivo pharmacology of GABAB receptor ligands. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of a drug with a relatively simple mechanism of action (baclofen) and a drug with a more complex mechanism of action [gamma-hydroxybutyrate (GHB)]. A number of studies have provided evidence that the behavioral effects of baclofen and GHB are mediated predominantly by GABAB receptors; however, there is growing evidence that the mechanisms mediating the effects of these two drugs are not identical. The differences between baclofen and GHB are relevant not only for understanding their distinct therapeutic and abuse-related effects, but also for understanding their susceptibility to positive modulatory effects, which could allow for a more selective modulation of the GABAB receptor system, thereby leading to safer and more effective therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ator, N. A., & Griffiths, R. R. (1983). Lorazepam and pentobarbital drug discrimination in baboons: Cross-drug generalization and interaction with Ro 15-1788. Journal of Pharmacology and Experimental Therapeutics, 226, 776–782.

    CAS  PubMed  Google Scholar 

  • Baker, L. E., Pynnonen, D., & Poling, A. (2004). Influence of reinforcer type and route of administration on gamma-hydroxybutyrate discrimination in rats. Psychopharmacology, 174, 220–227.

    Article  CAS  PubMed  Google Scholar 

  • Baker, L. E., Searcy, G. D., Pynnonen, D. M., & Poling, A. (2008). Differentiating the discriminative stimulus effects of gamma-hydroxybutyrate and ethanol in a three-choice drug discrimination procedure in rats. Pharmacology, Biochemistry and Behavior, 89, 598–607.

    Article  CAS  PubMed  Google Scholar 

  • Baker, L. E., Van Tilburg, T. J., Brandt, A. E., & Poling, A. (2005). Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic precursor, gamma-butyrolactone (GBL) in rats. Psychopharmacology, 181, 458–466.

    Article  CAS  PubMed  Google Scholar 

  • Banks, M. L., Hutsell, B. A., Blough, B. E., Poklis, J. L., & Negus, S. S. (2015). Preclinical assessment of lisdexamfetamine as an agonist medication candidate for cocaine addiction: Effects in rhesus monkeys trained to discriminate cocaine or to self-administer cocaine in a cocaine versus food choice procedure. International Journal of Neuropsychopharmacology, 18, 1–10.

    Article  CAS  Google Scholar 

  • Beveridge, T. J., Smith, H. R., & Porrino, L. J. (2013). Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats. Pharmacology, Biochemistry and Behavior, 106, 27–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bigelow, G. E., & Preston, K. L. (1992). Assessment of buprenorphine in a drug discrimination procedure in humans. NIDA Research Monograph, 121, 28–37.

    CAS  PubMed  Google Scholar 

  • Boja, J. W., & Schechter, M. D. (1990). Increased drug sensitivity in the drug discrimination procedure afforded by drug versus drug training. Psychopharmacology, 102, 221–226.

    Article  CAS  PubMed  Google Scholar 

  • Bonanno, G., & Raiteri, M. (1993). gamma-Aminobutyric acid (GABA) autoreceptors in rat cerebral cortex and spinal cord represent pharmacologically distinct subtypes of the GABAB receptor. Journal of Pharmacology and Experimental Therapeutics, 265, 765–770.

    CAS  PubMed  Google Scholar 

  • Bowery, N. G., Bettler, B., Froestl, W., Gallagher, J. P., Marshall, F., Raiteri, M., et al. (2002). International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: Structure and function. Pharmacological Reviews, 54, 247–264.

    Article  CAS  PubMed  Google Scholar 

  • Bowery, N. G., & Enna, S. J. (2000). gamma-Aminobutyric acid(B) receptors: First of the functional metabotropic heterodimers. Journal of Pharmacology and Experimental Therapeutics, 292, 2–7.

    CAS  PubMed  Google Scholar 

  • Bowery, N. G., Hill, D. R., Hudson, A. L., Doble, A., Middlemiss, D. N., Shaw, J., et al. (1980). (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature, 283, 92–94.

    Article  CAS  PubMed  Google Scholar 

  • Brandt, M. R., Cabansag, S. R., & France, C. P. (1997). Discriminative stimulus effects of l-alpha-acetylmethadol (LAAM), buprenorphine and methadone in morphine-treated rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 282, 574–584.

    CAS  PubMed  Google Scholar 

  • Callahan, P. M., & Appel, J. B. (1990). Differentiation between the stimulus effects of (+)-lysergic acid diethylamide and lisuride using a three-choice, drug discrimination procedure. Psychopharmacology, 100, 13–18.

    Article  CAS  PubMed  Google Scholar 

  • Carter, L. P., Chen, W., Coop, A., Koek, W., & France, C. P. (2006). Discriminative stimulus effects of GHB and GABA(B) agonists are differentially attenuated by CGP35348. European Journal of Pharmacology, 538, 85–93.

    Article  CAS  PubMed  Google Scholar 

  • Carter, L. P., Flores, L. R., Wu, H., Chen, W., Unzeitig, A. W., Coop, A., et al. (2003). The role of GABAB receptors in the discriminative stimulus effects of gamma-hydroxybutyrate in rats: Time course and antagonism studies. Journal of Pharmacology and Experimental Therapeutics, 305, 668–674.

    Article  CAS  PubMed  Google Scholar 

  • Carter, L. P., Koek, W., & France, C. P. (2009). Behavioral analyses of GHB: Receptor mechanisms. Pharmacology & Therapeutics, 121, 100–114.

    Article  CAS  Google Scholar 

  • Carter, L. P., Unzeitig, A. W., Wu, H., Chen, W., Coop, A., Koek, W., et al. (2004). The discriminative stimulus effects of gamma-hydroxybutyrate and related compounds in rats discriminating baclofen or diazepam: The role of GABA(B) and GABA(A) receptors. Journal of Pharmacology and Experimental Therapeutics, 309, 540–547.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Y., Menendez-Roche, N., & Sher, E. (2006). Differential modulation by the GABAB receptor allosteric potentiator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930) of synaptic transmission in the rat hippocampal CA1 area. Journal of Pharmacology and Experimental Therapeutics, 317, 1170–1177.

    Article  CAS  PubMed  Google Scholar 

  • Colombo, G., Agabio, R., Bourguignon, J., Fadda, F., Lobina, C., Maitre, M., et al. (1995a). Blockade of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS-382. Physiology & Behavior, 58, 587–590.

    Article  CAS  Google Scholar 

  • Colombo, G., Agabio, R., Carai, M. A., Lobina, C., Pani, M., Reali, R., et al. (2000). Characterization of the discriminative stimulus effects of gamma-hydroxybutyric acid as a means for unraveling the neurochemical basis of gamma-hydroxybutyric acid actions and its similarities to those of ethanol. Alcohol, 20, 237–245.

    Article  CAS  PubMed  Google Scholar 

  • Colombo, G., Agabio, R., Lobina, C., Reali, R., Fadda, F., & Gessa, G. L. (1995b). Symmetrical generalization between the discriminative stimulus effects of gamma-hydroxybutyric acid and ethanol: Occurrence within narrow dose ranges. Physiology & Behavior, 57, 105–111.

    Article  CAS  Google Scholar 

  • Colombo, G., Agabio, R., Lobina, C., Reali, R., & Gessa, G. L. (1998). Involvement of GABA(A) and GABA(B) receptors in the mediation of discriminative stimulus effects of gamma-hydroxybutyric acid. Physiology & Behavior, 64, 293–302.

    Article  CAS  Google Scholar 

  • Colpaert, F. C. (1978). Discriminative stimulus properties of narcotic analgesic drugs. Pharmacology, Biochemistry and Behavior, 9, 863–887.

    Article  CAS  PubMed  Google Scholar 

  • Colpaert, F. C., & Janssen, P. A. (1982). Factors regulating drug cue sensitivity: Limits of discriminability and the role of a progressively decreasing training dose in cocaine-saline discrimination. Neuropharmacology, 21, 1187–1194.

    Article  CAS  PubMed  Google Scholar 

  • Colpaert, F. C., Kuyps, J. J., Niemegeers, C. J., & Janssen, P. A. (1976). Discriminative stimulus properties of fentanyl and morphine: Tolerance and dependence. Pharmacology, Biochemistry and Behavior, 5, 401–408.

    Article  CAS  PubMed  Google Scholar 

  • Colpaert, F. C., Niemegeers, C. J., & Janssen, P. A. (1980a). Factors regulating drug cue sensitivity: Limits of discriminability and the role of a progressively decreasing training dose in fentanyl-saline discrimination. Journal of Pharmacology and Experimental Therapeutics, 212, 474–480.

    CAS  PubMed  Google Scholar 

  • Colpaert, F. C., Niemegeers, C. J., & Janssen, P. A. (1980b). Factors regulating drug cue sensitivity: The effect of training dose in fentanyl-saline discrimination. Neuropharmacology, 19, 705–713.

    Article  CAS  PubMed  Google Scholar 

  • Comer, S. D., France, C. P., & Woods, J. H. (1991). Training dose: Influences in opioid drug discrimination. NIDA Research Monograph, 116, 145–161.

    CAS  Google Scholar 

  • Dykstra, L. A., Bertalmio, A. J., & Woods, J. H. (1988). Discriminative and analgesic effects of mu and kappa opioids: In vivo pA2 analysis. Psychopharmacology Series, 4, 107–121.

    CAS  PubMed  Google Scholar 

  • Eckermann, K. A., Koek, W., & France, C. P. (2004). Chronic 1,4-butanediol treatment in rats: Cross-tolerance to gamma-hydroxybutyrate and (+/-)-baclofen. European Journal of Pharmacology, 484, 259–262.

    Article  CAS  PubMed  Google Scholar 

  • France, C. P., de Costa, B. R., Jacobson, A. E., Rice, K. C., & Woods, J. H. (1990). Apparent affinity of opioid antagonists in morphine-treated rhesus monkeys discriminating between saline and naltrexone. Journal of Pharmacology and Experimental Therapeutics, 252, 600–604.

    CAS  PubMed  Google Scholar 

  • France, C. P., & Woods, J. H. (1985). Opiate agonist-antagonist interactions: Application of a three-key drug discrimination procedure. Journal of Pharmacology and Experimental Therapeutics, 234, 81–89.

    CAS  PubMed  Google Scholar 

  • France, C. P., & Woods, J. H. (1989). Discriminative stimulus effects of naltrexone in morphine-treated rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 250, 937–943.

    CAS  PubMed  Google Scholar 

  • Gerak, L. R., & France, C. P. (2007). Time-dependent decreases in apparent pA2 values for naltrexone studied in combination with morphine in rhesus monkeys. Psychopharmacology, 193, 315–321.

    Article  CAS  PubMed  Google Scholar 

  • Gerak, L. R., & France, C. P. (2012). Quantitative analyses of antagonism: Combinations of midazolam and either flunitrazepam or pregnanolone in rhesus monkeys discriminating midazolam. Journal of Pharmacology and Experimental Therapeutics, 340, 742–749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarbe, T. U. (1976). Characteristics of pentobarbital discrimination in the gerbil: Transfer and antagonism. Psychopharmacology, 49, 33–40.

    CAS  PubMed  Google Scholar 

  • Kenakin, T. P. (1982). The Schild regression in the process of receptor classification. Canadian Journal of Physiology and Pharmacology, 60, 249–265.

    Article  CAS  PubMed  Google Scholar 

  • Koek, W., Carter, L. P., Lamb, R. J., Chen, W., Wu, H., Coop, A., et al. (2005). Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) in rats discriminating GHB from baclofen and diazepam. Journal of Pharmacology and Experimental Therapeutics, 314, 170–179.

    Article  CAS  PubMed  Google Scholar 

  • Koek, W., Chen, W., Mercer, S. L., Coop, A., & France, C. P. (2006). Discriminative stimulus effects of gamma-hydroxybutyrate: Role of training dose. Journal of Pharmacology and Experimental Therapeutics, 317, 409–417.

    Article  CAS  PubMed  Google Scholar 

  • Koek, W., Cheng, K., & Rice, K. C. (2013). Discriminative stimulus effects of the GABAB receptor-positive modulator rac-BHFF: Comparison with GABAB receptor agonists and drugs of abuse. Journal of Pharmacology and Experimental Therapeutics, 344, 553–560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koek, W., Flores, L. R., Carter, L. P., Lamb, R. J., Chen, W., Wu, H., et al. (2004). Discriminative stimulus effects of gamma-hydroxybutyrate in pigeons: Role of diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors. Journal of Pharmacology and Experimental Therapeutics, 308, 904–911.

    Article  CAS  PubMed  Google Scholar 

  • Koek, W., France, C. P., Cheng, K., & Rice, K. C. (2012). Effects of the GABAB receptor-positive modulators CGP7930 and rac-BHFF in baclofen- and gamma-hydroxybutyrate-discriminating pigeons. Journal of Pharmacology and Experimental Therapeutics, 341, 369–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koek, W., Mercer, S. L., & Coop, A. (2007). Cataleptic effects of gamma-hydroxybutyrate (GHB), its precursor gamma-butyrolactone (GBL), and GABAB receptor agonists in mice: Differential antagonism by the GABAB receptor antagonist CGP35348. Psychopharmacology, 192, 407–414.

    Article  CAS  PubMed  Google Scholar 

  • Koek, W., Mercer, S. L., Coop, A., & France, C. P. (2009). Behavioral effects of gamma-hydroxybutyrate, its precursor gamma-butyrolactone, and GABA(B) receptor agonists: Time course and differential antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). Journal of Pharmacology and Experimental Therapeutics, 330, 876–883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koek, W., & Slangen, J. L. (1982). The role of fentanyl training dose and of the alternative stimulus condition in drug generalization. Psychopharmacology, 76, 149–156.

    Article  CAS  PubMed  Google Scholar 

  • Krimmer, E. C., & Barry, H., III. (1979). Pentobarbital and chlordiazepoxide differentiated from each other and from nondrug. Communications in Psychopharmacology, 3, 93–99.

    CAS  PubMed  Google Scholar 

  • Lambert, N. A., & Wilson, W. A. (1993). Heterogeneity in presynaptic regulation of GABA release from hippocampal inhibitory neurons. Neuron, 11, 1057–1067.

    Article  CAS  PubMed  Google Scholar 

  • Lanza, M., Fassio, A., Gemignani, A., Bonanno, G., & Raiteri, M. (1993). CGP 52432: A novel potent and selective GABAB autoreceptor antagonist in rat cerebral cortex. European Journal of Pharmacology, 24, 191–195.

    Article  Google Scholar 

  • Li, J. X., Rice, K. C., & France, C. P. (2009). Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys: Antagonism and apparent pA2 analyses. Journal of Pharmacology and Experimental Therapeutics, 328, 976–981.

    Article  CAS  PubMed  Google Scholar 

  • Lobina, C., Agabio, R., Reali, R., Gessa, G. L., & Colombo, G. (1999). Contribution of GABA(A) and GABA(B) receptors to the discriminative stimulus produced by gamma-hydroxybutyric acid. Pharmacology, Biochemistry and Behavior, 64, 363–365.

    Article  CAS  PubMed  Google Scholar 

  • Mansbach, R. S., & Balster, R. L. (1991). Pharmacological specificity of the phencyclidine discriminative stimulus in rats. Pharmacology, Biochemistry and Behavior, 39, 971–975.

    Article  CAS  PubMed  Google Scholar 

  • Mathivet, P., Bernasconi, R., De Barry, J., Marescaux, C., & Bittiger, H. (1997). Binding characteristics of gamma-hydroxybutyric acid as a weak but selective GABAB receptor agonist. European Journal of Pharmacology, 321, 67–75.

    Article  CAS  PubMed  Google Scholar 

  • McMillan, D. E., Hardwick, W. C., & Li, M. (2002). Drug discrimination under concurrent variable-ratio variable-ratio schedules. Journal of Experimental Analysis of Behavior, 77, 91–104.

    Article  CAS  Google Scholar 

  • Metcalf, B. R., Stahl, J. M., Allen, J. D., Woolfolk, D. R., & Soto, P. L. (2001). Discrimination of gamma-hydroxybutyrate and ethanol administered separately and as a mixture in rats. Pharmacology, Biochemistry and Behavior, 70, 31–41.

    Article  CAS  PubMed  Google Scholar 

  • Nader, M. A., Winger, G., Woods, J. H., & Woolverton, W. L. (1991). Discriminative and reinforcing effects of brotizolam in rhesus monkeys. Psychopharmacology, 103, 166–171.

    Article  CAS  PubMed  Google Scholar 

  • Nielsen, J. F., Hansen, H. J., Sunde, N., & Christensen, J. J. (2002). Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen. Clinical Neurology and Neurosurgery, 104, 142–145.

    Article  PubMed  Google Scholar 

  • Nissbrandt, H., & Engberg, G. (1996). The GABAB-receptor antagonist, CGP 35348, antagonises gamma-hydroxybutyrate- and baclofen-induced alterations in locomotor activity and forebrain dopamine levels in mice. Journal of Neural Transmission, 103, 1255–1263.

    Article  CAS  PubMed  Google Scholar 

  • Parker, D. A., Marino, V., Ong, J., Puspawati, N. M., & Prager, R. H. (2008). The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABAB autoreceptors. Clinical and Experimental Pharmacology & Physiology, 35, 1113–1115.

    Article  CAS  Google Scholar 

  • Paronis, C. A., & Bergman, J. (1999). Apparent pA2 values of benzodiazepine antagonists and partial agonists in monkeys. Journal of Pharmacology and Experimental Therapeutics, 290, 1222–1229.

    CAS  PubMed  Google Scholar 

  • Rush, C. R., Kelly, T. H., Hays, L. R., & Wooten, A. F. (2002). Discrimnative-stimulus effects of modafinil in cocaine-trained humans. Drug and Alcohol Dependence, 67, 311–322.

    Article  CAS  PubMed  Google Scholar 

  • Sannerud, C. A., & Ator, N. A. (1995). Drug discrimination analysis of midazolam under a three-lever procedure: I. Dose-dependent differences in generalization and antagonism. Journal of Pharmacology and Experimental Therapeutics, 272, 100–111.

    CAS  PubMed  Google Scholar 

  • Schechter, M. D. (1997). Discrete versus cumulative dosing in dose-response discrimination studies. European Journal of Pharmacology, 326, 113–118.

    Article  CAS  PubMed  Google Scholar 

  • Seabrook, G. R., Howson, W., & Lacey, M. G. (1990). Electrophysiological characterization of potent agonists and antagonists at pre- and postsynaptic GABAB receptors on neurones in rat brain slices. British Journal of Pharmacology, 101, 949–957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sell, S. L., McMahon, L. R., & France, C. P. (2003). Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone. Journal of Pharmacology and Experimental Therapeutics, 306, 1167–1173.

    Article  CAS  PubMed  Google Scholar 

  • Shannon, H. E., & Holtzman, S. G. (1976a). Evaluation of the discriminative effects of morphine in the rat. Journal of Pharmacology and Experimental Therapeutics, 198, 54–65.

    CAS  PubMed  Google Scholar 

  • Shannon, H. E., & Holtzman, S. G. (1976b). Blockade of the discriminative effects of morphine in the rat by naltrexone and naloxone. Psychopharmacology, 50, 119–124.

    Article  CAS  PubMed  Google Scholar 

  • Shannon, H. E., & Holtzman, S. G. (1977). Further evaluation of the discriminative effects of morphine in the rat. Journal of Pharmacology and Experimental Therapeutics, 201, 55–66.

    CAS  PubMed  Google Scholar 

  • Shannon, H. E., & Holtzman, S. G. (1979). Morphine training dose: A determinant of stimulus generalization to narcotic antagonists in the rat. Psychopharmacology, 61, 239–244.

    Article  CAS  PubMed  Google Scholar 

  • Smith, M. A., Gergans, S. R., & Lyle, M. A. (2006). The motor-impairing effects of GABA(A) and GABA(B) agonists in gamma-hydroxybutyrate (GHB)-treated rats: Cross-tolerance to baclofen but not flunitrazepam. European Journal of Pharmacology, 552, 83–89.

    Article  CAS  PubMed  Google Scholar 

  • Snodgrass, S. H., & McMillan, D. E. (1991). Effects of schedule of reinforcement on a pentobarbital discrimination in rats. Journal of Experimental Analysis of Behavior, 56, 313–329.

    Article  CAS  Google Scholar 

  • Stolerman, I. P., & Mariathasan, E. A. (1990). Discrimination of an amphetamine-pentobarbitone mixture by rats in an AND-OR paradigm. Psychopharmacology, 102, 557–560.

    Article  CAS  PubMed  Google Scholar 

  • Stoops, W. W. (2006). Aripiprazole as a potential pharmacotherapy for stimulant dependence: Human laboratory studies with d-amphetamine. Experimental and Clinical Psychopharmacology, 14, 413–421.

    Article  CAS  PubMed  Google Scholar 

  • Walker, E. A., Makhay, M. M., House, J. D., & Young, A. M. (1994). In vivo apparent pA2 analysis for naltrexone antagonism of discriminative stimulus and analgesic effects of opiate agonists in rats. Journal of Pharmacology and Experimental Therapeutics, 271, 959–968.

    CAS  PubMed  Google Scholar 

  • Walker, E. A., Richardson, T. M., & Young, A. M. (1997). Tolerance and cross-tolerance to morphine-like stimulus effects of mu opioids in rats. Psychopharmacology, 133, 17–28.

    Article  CAS  PubMed  Google Scholar 

  • White, J. M., & Holtzman, S. G. (1981). Three-choice drug discrimination in the rat: Morphine, cyclazocine and saline. Journal of Pharmacology and Experimental Therapeutics, 217, 254–262.

    CAS  PubMed  Google Scholar 

  • Winger, G., & Herling, S. (1982). Discriminative stimulus effects of pentobarbital in rhesus monkeys: Tests of stimulus generalization and duration of action. Psychopharmacology, 76, 172–176.

    Article  CAS  PubMed  Google Scholar 

  • Winter, J. C. (1981). The stimulus properties of gamma-hydroxybutyrate. Psychopharmacology, 73, 372–375.

    Article  CAS  PubMed  Google Scholar 

  • Woolverton, W. L., & Nader, M. A. (1995). Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline. Psychopharmacology, 122, 230–236.

    Article  CAS  PubMed  Google Scholar 

  • Yamada, K., Yu, B., & Gallagher, J. P. (1999). Different subtypes of GABAB receptors are present at pre- and postsynaptic sites within the rat dorsolateral septal nucleus. Journal of Neurophysiology, 81, 2875–2883.

    CAS  PubMed  Google Scholar 

  • Young, A. M. (1991). Tolerance to drugs acting as discriminative stimuli. NIDA Research Monograph, 116, 197–211.

    CAS  Google Scholar 

Download references

Acknowledgments

Disclosures

Drs. Baladi and Carter are employed by Jazz Pharmaceuticals and have received stock awards and stock options exercisable for ordinary shares of Jazz Pharmaceuticals plc.

Author information

Authors and Affiliations

  1. Jazz Pharmaceuticals, Palo Alto, CA, 94304, USA

    Michelle G. Baladi & Lawrence P. Carter

  2. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Lawrence P. Carter

Authors
  1. Michelle G. Baladi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lawrence P. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence P. Carter .

Editor information

Editors and Affiliations

  1. Neuroscience Institute, National Research Council of Italy Neuroscience Institute, Cagliari, Italy

    Giancarlo Colombo

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Baladi, M.G., Carter, L.P. (2016). Drug Discrimination Studies for Investigations on the Mechanisms of Action of GABAB Receptor Ligands. In: Colombo, G. (eds) GABAB Receptor. The Receptors, vol 29. Humana Press, Cham. https://doi.org/10.1007/978-3-319-46044-4_9

Download citation

Publish with us

Policies and ethics

Search

Navigation