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Watson, J.; Guzzetti, S.; Franchi, C.; Di Clemente, A.; Burbassi, S.; Emri, Z.; Leresche, N.; Parri, H.R.; Crunelli, V.; Cervo, L. (2010)
Publisher: Cambridge University Press
Languages: English
Types: Article
Subjects: Conditioned place preference; GHB; Nucleus accumbens; Self-administration; Ventral tegmental area; Administration, Oral; Animals; Conditioning, Operant; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Microinjections; Nucleus Accumbens; Rats; Rats, Wistar; Self Administration; Sodium Oxybate; Ventral Tegmental Area; Pharmacology; Psychiatry and Mental Health; Pharmacology (medical), Settore BIO/14 - Farmacologia

Classified by OpenAIRE into

mesheuropmc: nervous system, psychological phenomena and processes, musculoskeletal, neural, and ocular physiology
Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons.
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    • Abanades S, Farre´ M, Barral D, Torrens M, et al. (2007). Relative abuse liability of gamma-hydroxybutyric acid, flunitrazepam, and ethanol in club drug users. Journal of Clinical Psychopharmacology 27, 625-638.
    • Addolorato G, Balducci G, Capristo E, Attilia ML, et al. (1999). Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome : a randomized comparative study versus benzodiazepine. Alcoholism : Clinical and Experimental Research 23, 1596-1604.
    • Baker DA, Specio SE, Tran-Nguyen LT, Neisewander JL (1998). Amphetamine infused into the ventrolateral striatum produces oral stereotypies and conditioned place preference. Pharmacology Biochemistry and Behavior 61, 107-111.
    • Beardsley PM, Balster RL, Harris LS (1996). Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB). Psychopharmacology (Berlin) 127, 315-322.
    • Bernasconi R, Mathivet P, Bischoff S, Marescaux C (1999). Gamma-hydroxybutyric acid : an endogenous neuromodulator with abuse potential? Trends in Pharmacological Science 20, 135-141.
    • Black J, Guilleminault C (2001). Medications for the treatment of narcolepsy. Expert Opinion on Emerging Drugs 6, 239-247.
    • Chambliss KL, Gibson KM (1992). Succinic semialdehyde dehydrogenase from mammalian brain : subunit analysis using polyclonal antiserum. International Journal of Biochemistry 24, 1493-1499.
    • Caine SB, Lintz R, Koob GF (1993). Intravenous drug self-administration techniques in animals. In : Sahgal EA (Ed.), Behavioral Neuroscience : A Practical Approach (pp. 117-143). Oxford IRL Press : Oxford.
    • Caine SB, Negus SS, Mello NK, Bergman J (1999). Effects of dopamine D(1-like) and D(2-like) agonists in rats that self-administer cocaine. Journal of Pharmacology and Experimental Therapeutics 291, 353-360.
    • Cam´ı J, Farre´ M (2003). Drug addiction. New England Journal of Medicine 349, 975-986.
    • Caputo F, Addolorato G, Trevisani F, Bernardi M (2005). Gamma-hydroxybutyrate as a treatment for alcoholism. Lancet 366, 981-982.
    • Carr DB, Sesack SR (2000). GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex. Synapse 38, 114-123.
    • Carter LP, Richards BD, Mintzer MZ, Griffiths RR (2006). Relative abuse liability of GHB in humans : a comparison of psychomotor, subjective, and cognitive effects of supratherapeutic doses of triazolam, pentobarbital, and GHB. Neuropsychopharmacology 31, 2537-2551.
    • Cash CD (1994). Gamma-hydroxybutyrate : an overview of the pros and cons for it being a neurotransmitter and/or a useful therapeutic agent. Neuroscience Biobehavioral Reviews 18, 291-304.
    • Cervo L, Samanin R (1995). Effects of dopaminergic and glutamatergic receptor antagonists on the acquisition and expression of cocaine conditioning place preference. Brain Research 673, 242-250.
    • Cervo L, Pozzi L, Samanin R (1996). 5-HT3 receptor antagonists do not modify cocaine place conditioning or the rise in extracellular dopamine in the nucleus accumbens of rats. Pharmacology Biochemistry and Behavior 55, 33-37.
    • Cervo L, Mukherjee S, Bertaglia A, Samanin R (1997). Protein kinases A and C are involved in the mechanisms underlying consolidation of cocaine place conditioning. Brain Research 775, 30-36.
    • Cervo L, Carnovali F, Stark JA, Mennini T (2003). Cocaine-seeking behavior in response to drug-associated stimuli in rats : involvement of D3 and D2 dopamine receptors. Neuropsychopharmacology 28, 1150-1159.
    • Cervo L, Rozio M, Ekalle-Soppo CB, Carnovali F, et al. (2002). Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats. Psychopharmacology (Berlin) 163, 142-150.
    • Cervo L, Burbassi S, Colovic M, Caccia S (2005). Selective antagonist at D3 receptors, but not non-selective partial agonists, influences the expression of cocaine-induced conditioned place preference in free-feeding rats. Pharmacology Biochemistry and Behavior 82, 727-734.
    • Colombo G, Agabio R, Balaklievskaia N, Diaz G, et al. (1995). Oral self-administration of gamma-hydroxybutyric acid in the rat. European Journal Pharmacology 285, 103-107.
    • Crunelli V, Emri Z, Leresche N (2006). Unravelling the brain targets of gamma-hydroxybutyric acid. Current Opinion Pharmacology 6, 44-52.
    • Cruz HG, Ivanova T, Lunn ML, Stoffel M, et al. (2004). Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system. Nature Neuroscience 7, 153-159.
    • Degenhardt L, Copeland J, Dillon P (2005). Recent trends in the use of ' club drugs' : an Australian review. Substance Use & Misuse 40, 1241-1256.
    • Di Chiara G, Imperato A (1988). Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proceedings of the National Academy of Sciences USA 85, 5274-5278.
    • EMCDDA (2008). GHB and its precursor GBL : an emerging trend case study. European Monitoring Centre for Drugs and Drug Addiction, Lisbon (http://www.emcdda. europa.eu/publications/thematic-papers/ghb).
    • Fattore L, Cossu G, Martellotta MC, Deiana S, Fratta W (2001). Baclofen antagonises intravenous selfadministration of gamma-hydroxybutyric acid in mice. Neuroreport 12, 2243-2246.
    • Fibiger HC, Phillips AG (1988). Mesocorticolimbic dopamine systems and reward. Annals of the New York Academy of Sciences 537, 206-215.
    • Finlay JM, Szostak C, Fibiger HC (1989). Further characterization of intravenous self-administration of midazolam in the rat. Behavioral Pharmacology 1, 13-23.
    • Gallimberti L, Canton G, Gentile N, Ferri M, et al. (1989). Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet 30, 787-789.
    • Gardner EL, Lawinson JH (1993). Drug craving and positive/negative hedonic brain substrates activated by addicting drugs. Seminars in Neuroscience 5, 359-368.
    • Johnson SW, North RA (1992). Two types of neurones in the rat ventral tegmental area and their synaptic inputs. Journal of Physiology (London) 450, 455-468.
    • Kalivas PW (1993). Neurotransmitter regulation of dopamine neurons in the ventral tegmental area. Brain Research. Brain Research Reviews 18, 75-113.
    • Kam PC, Yoong FF (1998). Gamma-hydroxybutyric acid : an emerging recreational drug. Anaesthesia 53, 1195-1198.
    • Kaufman EE, Nelson T (1987). Evidence for the participation of a cytosolic NADP+-dependent oxidoreductase in the catabolism of gamma-hydroxybutyrate in vivo. Journal of Neurochemistry 48, 1935-1941.
    • Koob GF (1992). Neural mechanisms of drug reinforcement. Annals of the New York Academy of Sciences 654, 171-191.
    • Koob GF, Sanna PP, Bloom FE (1998). Neuroscience of addiction. Neuron 21, 467-476.
    • Itzhak Y, Syed FA (2002). Repeated administration of gamma-hydroxybutyric acid (GHB) to mice. Assessment of the sedative and rewarding effects of GHB. Annals of the New York Academy of Science 965, 451-460.
    • Laborit H, Jouany J, Gerard J, Fabiani F (1960). Generalities concerning the experimental study and clinical use of sodium gammahydroxybutyrate. Agressologie 1, 397-406.
    • Laboue`be G, Lomazzi M, Cruz HG, Creton C, et al. (2007). RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nature Neuroscience 10, 1559-1568.
    • Lingenhoehl K, Brom R, Heid J, Beck P, et al. (1999). Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors. Neuropharmacology 38, 1667-1673.
    • Lobina C, Colombo G, Brunetti G, Diaz G, et al. (2001). Procedure of bidirectional selective outbreeding for production of two rat lines differing in sensitivity to the sedative/hypnotic effect of gamma-hydroxybutyric acid. Brain Research. Brain Research Protocols 8, 74-81.
    • Lu¨ scher C, Ungless MA (2006). The mechanistic classification of addictive drugs. PLoS Medicine 3, e437.
    • Maitre M (1997). The gamma-hydroxybutyrate signalling system in brain : organization and functional implications. Progress in Neurobiology 51, 337-361.
    • Maldonado R (2003). The neurobiology of addiction. Journal of Neural Transmission (Suppl.) 66, 1-14.
    • Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W (1998). Intravenous self-administration of gammahydroxybutyric acid in drug-naive mice. European Journal Neuropsychopharmacology 8, 293-296.
    • Martellotta MC, Fattore L, Cossu G, Fratta W (1997). Rewarding properties of gamma-hydroxybutyric acid : an evaluation through place preference paradigm. Psychopharmacology (Berlin) 132, 1-5.
    • Mathivet P, Bernasconi R, De Barry J, Marescaux C, Bittiger H (1997). Binding characteristics of gammahydroxybutyric acid as a weak but selective GABAB receptor agonist. European Journal of Pharmacology 321, 67-75.
    • Miotto K, Darakjian J, Basch J, Murray S, et al. (2001). Gamma-hydroxybutyric acid : patterns of use, effects and withdrawal. American Journal on Addictions 10, 232-241.
    • Nava F, Premi S, Manzato E, Campagnola W, et al. (2007). Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics : an open study vs. diazepam. American Journal of Drug and Alcohol Abuse 33, 379-392.
    • Overton DA (1978). Basic mechanisms of state-dependent learning. Psychopharmacology Bulletin 14, 67-68.
    • Pardi D, Black J (2006). Gamma-hydroxybutyrate/sodium oxybate : neurobiology, and impact on sleep and wakefulness. CNS Drugs 20, 993-1018.
    • Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates, 4th edn. San Diego : Academic Press.
    • Pistis M, Muntoni AL, Pillolla G, Perra S, et al. (2005). Gamma-hydroxybutyric acid (GHB) and the mesoaccumbens reward circuit : evidence for GABA(B) receptor-mediated effects. Neuroscience 131, 465-474.
    • Ricaurte GA, McCann UD (2005). Recognition and management of complications of new recreational drug use. Lancet 365, 2137-2145.
    • Robbins TW, Everitt BJ (1999). Drug addiction : bad habits add up. Nature 398, 567-570.
    • Schwartz RH, Milteer R, LeBeau MA (2000). Drug-facilitated sexual assault (' date rape'). Southern Medical Journal 93, 558-561.
    • Snead 3rd OC, Gibson KM (2005). Gamma-hydroxybutyric acid. New England Journal of Medicine 352, 2721-2732.
    • Sumnall HR, Woolfall K, Edwards S, Cole JC, Beynon CM (2008). Use, function, and subjective experiences of gamma-hydroxybutyrate (GHB). Drug and Alcohol Dependence 92, 286-290.
    • Tunnicliff G, Raess BU (2002). Gamma-hydroxybutyrate (orphan medical). Current Opinion in Investigational Drugs 3, 278-283.
    • Tzschentke TM (2007). Measuring reward with the conditioned place preference (CPP) paradigm : update of the last decade. Addiction Biology 12, 227-462.
    • Van Bockstaele EJ, Pickel VM (1995). GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain. Brain Research 682, 215-221.
    • Varela M, Nogue´ S, Oro´ s M, Miro´ O (2004). Gamma hydroxybutirate use for sexual assault. Emergency Medicine Journal 21, 255-256.
    • Watson J, Guzzetti S, Burbassi S, Emri Z, et al. (2007). Gamma-hydroxybutyrate induces conditioned place preference but does not maintain self-administration in wistar rats. Neuroscience Meeting Planner. San Diego, CA : Society for Neuroscience [online].
    • Weingartner H, Murphy D, Stillman RC (1978). Drug and mood state-specific encoding and retrieval of experience. NIDA Research Monographs 19, 210-223.
    • Wise RA, Bozarth MA (1987). A psychomotor stimulant theory of addiction. Psychology Review 94, 469-492.
    • Wong CG, Gibson KM, Snead III OC (2004). From the street to the brain : neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends in Pharmacological Sciences 25, 29-34.
    • Woolverton WL, Rowlett JK, Winger G, Woods JH, et al. (1999). Evaluation of the reinforcing and discriminative stimulus effects of gamma-hydroxybutyrate in rhesus monkeys. Drug Alcohol Dependence 54, 137-143.
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