Differential involvement of gabaa and gabab receptors in propofol self-administration in rats

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ABSTRACT AIM: Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABAA antagonist and GABAB agonist on propofol reinforcement. METHODS:


Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio (FR1) schedule of reinforcement for 14 d. In a separate set of


experiments, food-maintained self-administration under a fixed ratio (FR5) schedule and locomotor activities of Sprague-Dawley rats were examined. RESULTS: GABAA receptor antagonist


bicuculline (0.25 mg/kg, ip) significantly increased the number of injections and active responses. Pretreatment with GABAB receptor agonist baclofen (3 mg/kg, ip) significantly decreased


the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen (50 and 100 ng/side) into the ventral tegmental area (VTA)


significantly decreased the number of active responses and total infusions of propofol. Neither baclofen (1-3 mg/kg, ip) nor bicuculline (0.25-1 mg/kg, ip) affected food-maintained responses


or motor activities. CONCLUSION: Propofol maintains its reward properties partially through GABAA receptor activation. Stimulation of GABAB receptors in VTA may counteract the reinforcing


properties of propofol. SIMILAR CONTENT BEING VIEWED BY OTHERS INVOLVEMENT OF THE DOPAMINERGIC SYSTEM IN THE REWARD-RELATED BEHAVIOR OF PREGABALIN Article Open access 19 May 2021 ACTIVATION


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RECEPTOR ANTAGONISM ATTENUATES REINSTATEMENT OF ALCOHOL-SEEKING THROUGH MODULATION OF THE MESOLIMBIC CIRCUITRY IN MALE AND FEMALE ALCOHOL-PREFERRING RATS Article 20 July 2021 INTRODUCTION


Propofol (2, 6-disopropylphenol) is an intravenous, short-acting anesthetic that has been widely used for sedation and anesthesia. Clinical surveys reveal that propofol may have abuse


potential and dependency1. The abuse potential of propofol has also been demonstrated in preclinical studies using conditioned place preference (CPP)2, 3 and self-administration4, which are


the classic methods for the evaluation of the psychodependence of drugs. There are two types of neurons within the ventral tegmental area (VTA), primary dopaminergic projection neurons and


secondary γ-aminobutyric acid (GABA) inhibitory interneurons. The mesolimbic dopamine system, which originates in the VTA and connects to the nucleus accumbens (NAc), is a critical component


of reward and addiction. All drugs of abuse enhance the activity of the mesolimbic dopaminergic circuit of reward, which leads to the release of dopamine (DA) in the NAc5, 6. The release of


DA in the NAc indicates that the reinforcement potential of propofol may account for the regulation of the activity of the reward pathway. Both GABAA and GABAB receptor subtypes have been


identified within the VTA. The activation of GABAA on GABAergic interneurons increases the activity of dopamine neurons in the VTA through disinhibition7, 8. In contrast, GABAergic neurons


dampen DA neurons via inhibitory GABAB receptors on dopaminergic VTA neurons9. The microinjection of baclofen, a GABAB receptor agonist, into the VTA reduces heroin-induced DA release in the


NAc and inhibits heroin and morphine self-administration in a dose-dependent manner10. However, the role of each GABA receptor subtype in propofol reinforcement is not clear. Therefore, the


present study examined the effects of baclofen and bicuculline on propofol reinforcement using intravenous self-administration. MATERIALS AND METHODS ANIMALS Experiments were performed in


male Sprague-Dawley rats (280–300 g) that were purchased from the Experimental Animal Center of Zhejiang Province (Hangzhou, China). Rats were housed individually in home cages in a


temperature-controlled ventilated colony room with a reversed 12–12 h light/dark cycle (lights on at 7:00 pm). _Ad libitum_ food and water were provided in the home cage. The Institutional


Animal Care and Use Committee of Zhejiang Province approved all procedures. Animal care was provided by trained vivarium staff at the Laboratory of Ningbo Addiction Research and Treatment


Center (Ningbo, China). All animals were euthanized by carbon dioxide inhalation after pentobarbital anesthesia at the termination of experiments. DRUGS Propofol (10 mg/mL; Diprivan,


Astrazeneca, Italy) was prepared immediately before use and was injected intravenously. The propofol dose (1.7 mg/kg per infusion) that was used for the self-administration experiments was


based on a previous study4. Baclofen and bicuculline were purchased from Sigma Chemical Co (St Louis, USA). Both drugs were dissolved in sterile saline. APPARATUS Thirty-two custom-made


operant Plexiglas boxes (Ningbo Addiction Research and Treatment Center, China) were used for propofol training as described previously10. Briefly, each box was equipped with two nose-poke


apparatuses that were located 5 cm above the floor. There was a green LED light inside of each nose-poke hole. A house light (28 V, 0.1 mA) was situated on the wall above the nose-poke


holes. Drug solution was delivered through Tygon tubing that was protected by a leash assembly and suspended through the ceiling of the chamber from a plastic fluid swivel. The leash


assembly was modified to fit a custom-made fluid connector that was fixed on the animal's jacket. The Tygon tubing was attached to a syringe pump that delivered fluid at a speed of 1.2


mL/min using a 5-mL syringe. Experimental events were controlled by an IBM-compatible PC using an MED Associates interface and running self-programmed software written in Borland Delphi 6.0.


SURGERY The rats were surgically implanted with chronic indwelling intravenous catheters under sodium pentobarbital anesthesia using a previously described method10. The catheters were


flushed daily with a 0.2 mL saline-heparin solution (25 U/mL heparin) to maintain catheter patency. The rats were treated post-surgically with penicillin B for 5 d to prevent infection. All


of the animals were allowed to recover for at least 7 d10. In some experiments, bilateral guide cannulae (20-gauge Small Parts Inc, Roanoke, VA, USA) were implanted in the VTA (6.0 mm


posterior to bregma, 1.0 mm lateral to midline, and 7.8 mm ventral to the surface of the cortex using a 10° angle) according to a previously described method11. Guide cannulae were lowered


into place and attached to the skull via dental acrylic. Obturators were extended 0.5 mm beyond the tip of each cannula to prevent obstruction by debris. MICROINJECTION PROCEDURE Animals


that had been trained for 14 d received microinjections beginning on d 15. Obturators were removed, and bilateral infusion cannulae were inserted to extend 0.5 mm beyond the tip of the guide


cannulae. All injections into the VTA were delivered using a microinjection pump (MD-1001, Bioanalytical System Inc, West Lafayette, IN, USA) in a volume of 0.5 μL/side over 5 min. PROPOFOL


SELF-ADMINISTRATION TRAINING The rats were trained to self-administer drugs as described previously10. For each daily 3 h training session, the rats were moved from their home cages to the


operant chambers, and their connectors were attached to the infusion lines. Each session started with the illumination of the green light inside of the active nose-poke hole. The rats


received a single propofol infusion (1.7 mg/kg per infusion) following the completion of the ratio requirement (FR1) in the active nose-poke hole. Each infusion was paired with a 5 s


illumination of the house light and the noise of the infusion pump. A time-out period was imposed for 30 s, during which further responses produced no programmed consequences. However, these


responses were recorded. Illumination of the green light in the active nose-poke hole signaled the end of the 30 s timeout period. Responses in the inactive nose-poke hole produced no


programmed consequences. The sessions ended after 3 h or 50 propofol infusions, which ever event occurred first. SUCROSE SELF-ADMINISTRATION TRAINING The rats were trained to nose poke for


sucrose pellets under a fixed ratio (FR5) schedule of reinforcement daily 1-h session for 7 d. The paradigm for sucrose self-administration was similar to the paradigm for heroin


self-administration except that rats received a 45 mg sucrose pellet (Dustless precision pellets, Bio-Serv, NJ) that was delivered via a sucrose cup. During the session, each nose-poke in


the active hole resulted in the delivery of a food pellet only. Nose pokes in the inactive hole had no programmed consequence. Active nose-poke responses, inactive nose-poke responses, and


the number of sucrose pellets that were earned during each training session were recorded by a computer. Twenty minutes prior to the session on d 8, the trained rats received saline,


baclofen (1.0, 2.0 or 3.0 mg/kg, ip), or bicuculline (0.25, 0.5, or 1.0 mg/kg, ip). LOCOMOTOR TEST AFTER WITHDRAWAL We examined the effects of the intraperitoneal administration of either


baclofen or bicuculline on locomotion in a novel context to further assess the possible nonspecific effects of baclofen or bicuculline on general activity. The locomotor activity of naïve


rats (_n_=8 in each groups) was monitored for 3 h. The total distance traveled was recorded and analyzed as the measure of locomotion using MED Associates SOF-811 Open-field Activity


Software. HISTOLOGY The rats were anesthetized and transcardially perfused with phosphate-buffered saline followed by a 4% polyformaldehyde solution. The brains were sectioned in the coronal


plane to a thickness of 50 μm using a Cryostat Microtome (Leica CM1850; Leica, Wetzlar, Germany). The placement of the cannula tip for infusions was located using light microscopy and


mapped onto a schematic diagram of the rat brain using a previously published method11. Only animals with a proper functioning cannula and a correct location of the probe were included in


the study. SPECIFIC EXPERIMENTS EXPERIMENT 1 Rats were trained for propofol self-administration (1.7 mg/kg per infusion) for 14 d. The rats (_n_=24) were randomly assigned to one of 4 groups


and were injected with vehicle, 1.0 mg/kg, 2.0 mg/kg, or 3.0 mg/kg (ip) baclofen 20 min prior to testing. EXPERIMENT 2 The rats (_n_=24) underwent the 14-d training and were then injected


with vehicle or 0.25 mg/kg, 0.5 mg/kg, or 1.0 mg/kg (ip) bicuculline 20 min prior to testing. EXPERIMENT 3 Bilateral microinjections were performed into VTA as described above. The rats


(_n_=6 in each group) were placed into the self-administration chambers 10 min after intra-VTA baclofen (50 and 100 ng/side) or vehicle injection. Self-administration was examined as


described above. STATISTICAL ANALYSIS The number of infusions or responses in active or inactive holes during self-administration was analyzed using one-way ANOVA. A Newman-Keuls multiple


comparison with an alpha level of 0.05 was used for _post hoc_ comparisons between group means. RESULTS SYSTEMIC PRETREATMENT WITH BACLOFEN DECREASED PROPOFOL SELF-ADMINISTRATION The animals


exhibited reliable propofol self-administration, which was indicated by the increase in active responses and infusions during the acquisition, and maintained stable self-administration


during the late training sessions. ANOVA revealed a significant main effect of baclofen treatment on the number of active responses [_F_(3, 20)=3.32, _P_<0.05] (Figure 1A) and the number


of infusions [_F_(3, 20)=8.1, _P_<0.05] (Figure 1B). There was no significant difference in the number of inactive nose-poke responses between the groups [_F_(3, 20)=0.99, _P_>0.05]


(Figure 1A). Multiple comparisons showed that 3.0 mg/kg baclofen decreased the number of active responses compared to the control group (_P_<0.01) (Figure 1A). Baclofen at doses of 2.0 or


3.0 mg/kg decreased the number of infusions compared to the control group (_P_<0.05, _P_<0.01) (Figure 1B). SYSTEMIC PRETREATMENT WITH BICUCULLINE ENHANCED PROPOFOL


SELF-ADMINISTRATION ANOVA revealed a main effect of bicuculline treatment in the number of active responses [_F_(3, 20)=3.66, _P_<0.05] (Figure 2A) and the number of infusions [_F_(3,


20)=3.18, _P_<0.05] (Figure 2B). There was no difference of the number of inactive nose-poke responses between the groups [_F_(3, 20)=1.43, _P_>0.05] (Figure 2A). Multiple comparisons


demonstrated that 0.25 mg/kg bicuculline increased the number of active responses compared to the control group (_P_<0.01) (Figure 2A). Bicuculline at doses of 0.25 or 0.5 mg/kg increased


the number of infusions compared to the control group (_P_<0.01, _P_<0.05) (Figure 2B). MICROINJECTION OF BACLOFEN INTO THE VTA INHIBITED PROPOFOL SELF-ADMINISTRATION ANOVA revealed a


main effect of baclofen infusion into the VTA on the number of active responses [_F_(2, 15)=21.23, _P_<0.05] (Figure 3A) and the number of infusions [_F_(2, 15)=63.51, _P_<0.05]


(Figure 3B). There was no difference in the number of inactive nose-poke responses among the groups [_F_(2, 15)=0.081, _P_>0.05] (Figure 3A). Multiple comparisons demonstrated that both


doses of baclofen significantly decreased the number of active responses (_P_<0.01) (Figure 3A) and the number of infusions (_P_<0.01) (Figure 3B). NEITHER BACLOFEN NOR BICUCULLINE


AFFECTED FOOD-MAINTAINED BEHAVIOR OR LOCOMOTOR ACTIVITY One-way ANOVA revealed no apparent variance of baclofen treatment on the number of active [_F_(3, 24)=1.27, _P_>0.05] or inactive


nose-poke responses [_F_(3, 24)=1.36, _P_>0.05] or the number of sucrose pellets in food-maintained testing [_F_(3, 24)=0.32, _P_>0.05] (Figure 4A). Pretreatment with bicuculline did


not alter the number of active [_F_(3, 24)=0.94, _P_>0.05] or inactive nose-poke responses [_F_(3, 24)=1.9, _P_>0.05) or the number of sucrose pellets in food-maintained testing


[_F_(3, 24)=0.32, _P_>0.05] (Figure 5A). Pretreatment with either baclofen [_F_(3, 28)=1.53, _P_>0.05] (Figure 4B) or bicuculline [_F_(3, 28)=0.60, _P_>0.05] (Figure 5B) did not


affect the locomotor activity. DISCUSSION The main findings of this study are that bicuculline pretreatment at a lower dose increased the active responses and infusions of propofol


self-administration. However, baclofen pretreatment using a systemic or intra-VTA infusion reduced the active responses and infusions of propofol self-administration in a dose-dependent


manner in rats. Neither bicuculline nor baclofen affected food-maintained responses or locomotor activities. These results suggest that the action of bicuculline or baclofen on propofol


reinforcement cannot account for the impairment of coordinated motor ability. Drugs of abuse enhance DA release in the NAc via a disinhibition of GABAergic neurons in the VTA12. Propofol is


a positive allosteric modulator of the GABAA receptor. Benzodiazepines have recently been shown to increase the firing of DA neurons in the VTA via the positive modulation of GABAA receptors


on nearby interneurons7. In the present study, a low dose of bicuculline, an antagonist of GABAA receptors, significantly increased propofol self-administration, which suggests a


compensatory enhanced behavioral response as a result of the partial reversal of GABAA activation by propofol. Both pre-synaptic and post-synaptic GABAA receptors exist in the VTA. The


activation of pre-synaptic GABAA receptors leads to a decrease in GABA release from GABAergic interneurons and a subsequent increase in dopaminergic neurons. However, the activation of


post-synaptic GABAA receptors may reduce the activity of dopaminergic neurons13. A large dose of bicuculline did not affect propofol reinforcement, which may be explained by the blockade of


post-synaptic GABAA receptors. The present results are consistent with previous reports that the disinhibition of GABAA receptors triggers drug-evoked synaptic plasticity in excitatory


afferents that synapse on dopaminergic neurons, which underlies drug reinforcement7, 14. The capacity of GABAB receptors to modulate the DA projection from the VTA to the NAc has been the


subject of much research. GABAB receptor agonists reduce the activity of the mesolimbic DA system via direct actions on dopaminergic VTA neurons15, 16. The present results showed that the


systemic administration of the GABAB receptor agonist baclofen inhibited propofol self-administration in a dose-dependent manner. This result suggests that GABAB receptors regulate the


reinforcement of propofol. The results of this study are consistent with those of previous studies of other addictive drugs17, 18, 19, 20. For example, baclofen inhibits morphine and heroin


self-administration in rats10, 21. Additionally, baclofen pretreatment antagonizes the morphine-induced increase in DA levels in the NAc, which is mediated by GABAB receptors22. The majority


of VTA GABAB receptors are localized on dopaminergic neurons23. The present results also showed that an intra-VTA injection of baclofen reduced propofol self-administration, which is


consistent with a previous report that the microinjection of baclofen into the VTA, but not into the NAc, decreases opiate reinforcement21, 24. The inhibitory action of baclofen was blocked


by an intra-VTA infusion of a GABAB receptor antagonist21. Moreover, the inhibitory action of systemically administered baclofen suggests that baclofen acted on GABAB receptors on


dopaminergic neurons within the VTA to inhibit propofol reinforcement. In conclusion, the present data provided evidence that propofol maintains its reward properties partially through the


activation of GABAA receptors, but stimulation of the GABAB receptors in the VTA may counteract the reinforcing of properties of propofol. AUTHOR CONTRIBUTION Bo YANG, Wen-hua ZHOU, and


Qing-quan LIAN designed the studies; Bo YANG, Ben-fu WANG, Miao-jun LAI, Fu-qiang ZHANG, and Xiao-wei YANG performed the studies; Bo YANG, and Wen-hua ZHOU analyzed the data; Bo YANG,


Wen-hua ZHOU, and Qing-quan LIAN wrote the manuscript. REFERENCES * Roussin A, Montastruc JL, Lapeyre-Mestre M . Pharmacological and clinical evidences on the potential for abuse and


dependence of propofol: a review of the literature. _Fundam Clin Pharmacol_ 2007; 21: 459–66. Article  CAS  PubMed  Google Scholar  * Pain L, Oberling P, Sandner G, Di Scala G . Effect of


propofol on affective state as assessed by place conditioning paradigm in rats. _Anesthesiology_ 1996; 85: 121–8. Article  CAS  PubMed  Google Scholar  * Pain L, Oberling P, Sandner G, Di


Scala G . Effect of midazolam on propofol-induced positive affective state assessed by place conditioning in rats. _Anesthesiology_ 1997; 87: 935–43. Article  CAS  PubMed  Google Scholar  *


LeSage MG, Stafford D, Glowa JR . Abuse liability of the anesthetic propofol: self-administration of propofol in rats under fixed-ratio schedules of drug delivery. _Psychopharmacology


(Berl)_ 2000; 153: 148–54. Article  CAS  Google Scholar  * Wise RA . Dopamine, learning and motivation. _Nat Rev Neurosci_ 2004; 5: 483–94. Article  CAS  PubMed  Google Scholar  * Pain L,


Gobaille S, Schleef C, Aunis D, Oberling P . _In vivo_ dopamine measurements in the nucleus accumbens after nonanesthetic and anesthetic doses of propofol in rats. _Anesth Analg_ 2002; 95:


915–9. CAS  PubMed  Google Scholar  * Tan KR, Brown M, Labouèbe G, Yvon C, Creton C, Fritschy JM, _et al_. Neural bases for addictive properties of benzodiazepines. _Nature_ 2010; 463:


769–74. Article  CAS  PubMed  PubMed Central  Google Scholar  * Xi ZX, Stein EA . Nucleus accumbens dopamine release modulation by mesolimbic GABAA receptors-an _in vivo_ electrochemical


study. _Brain Research_ 1998; 798: 156–65. Article  CAS  PubMed  Google Scholar  * Cousins MS, Roberts DC, de Wit H . GABAB receptor agonists for the treatment of drug addiction: a review of


recent findings. _Drug Alcohol Depend_ 2002; 65: 209–20. Article  CAS  PubMed  Google Scholar  * Yoon SS, Lee BH, Kim HS, Choi KH, Yun J, Jang EY, _et al_. Potential roles of GABA receptors


in morphine self-administration in rats. _Neurosci Lett_ 2007; 428: 33–7. Article  CAS  PubMed  Google Scholar  * Zhou W, Liu H, Zhang F, Tang S, Zhu H, Lai M, _et al_. Role of


acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues. _Neuroscience_ 2007; 144: 1209–18. Article  CAS  PubMed  Google


Scholar  * Johnson SW, North RA . Opioids excite dopamine neurons by hyperpolarization of local interneurons. _J Neurosci_ 1992; 12: 483–8. Article  CAS  PubMed  PubMed Central  Google


Scholar  * McBride WJ, Murphym JM, Ikemoto S . Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. _Behav Brain Res_


1999; 101: 129–52. Article  CAS  PubMed  Google Scholar  * Laviolette, SR, Gallegos RA, Henriksen SJ, van der Kooy D . Opiate state controls bi-directional reward signaling via GABAA


receptors in the ventral tegmental area. _Nature Neurosci_ 2004; 7: 160–9. Article  CAS  PubMed  Google Scholar  * Panagis G, Kastellakis A . The effects of ventral tegmental administration


of GABAA, GABAB, NMDA and AMPA receptor agonists on ventral pallidum self-stimulation. _Behav Brain Res_ 2002; 131: 115–23. Article  CAS  PubMed  Google Scholar  * Westerink BH, Enrico P,


Feimann J, De Vries JB . The pharmacology of mesocortical dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and prefrontal cortex of the rat brain. _J


Pharmacol Exp Ther_ 1998; 285: 143–54. CAS  PubMed  Google Scholar  * Roberts DC, Andrews MM . Baclofen suppression of cocaine self-administration: demonstration using a discrete trials


procedure. _Psychopharmacology (Berl)_ 1997; 131: 271–7. Article  CAS  Google Scholar  * Shoaib M, Swanner LS, Beyer CE, Goldberg SR, Schindler CW . The GABAB agonist baclofen modifies


cocaine self-administration in rats. _Behav Pharmacol_ 1998; 9: 195–206. CAS  PubMed  Google Scholar  * Walker BM, Koob GF . The gamma-aminobutyric acid-B receptor agonist baclofen


attenuates responding for ethanol in ethanol-dependent rats. _Alcohol Clin Exp Res_ 2007; 31: 11–8. Article  CAS  PubMed  PubMed Central  Google Scholar  * Brebner K, Phelan R, Roberts DC .


Intra-VTA baclofen attenuates cocaine self-administration on a progressive ratio schedule of reinforcement. _Pharmacol Biochem Behav_ 2000; 66: 857–62. Article  CAS  PubMed  Google Scholar 


* Xi ZX, Stein EA . Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release. _J Pharmacol Exp Ther_ 1999; 290: 1369–74. CAS  PubMed  Google Scholar  * Fadda P,


Scherma M, Fresu A, Collu M, Fratta W . Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat. _Synapse_ 2003; 50: 1–6. Article  CAS


  PubMed  Google Scholar  * Margeta-Mitrovic M, Mitrovic I, Riley RC, Jan LY, Basbaum AI . Immunohistochemical localization of GABAB receptors in the rat central nervous system. _J Com


Neurol_ 1999; 405: 299–321. Article  CAS  Google Scholar  * Sahraei H, Amiri YA, Haeri-Rohani A, Sepehri H, Salimi SH, Pourmotabbed A, _et al_. Different effects of GABAergic receptors


located in the ventral tegmental area on the expression of morphine-induced conditioned place preference in rat. _Eur J Pharmacol_ 2005; 524: 95–101. Article  CAS  PubMed  Google Scholar 


Download references ACKNOWLEDGEMENTS This study was supported in part by the National Natural Science Foundation of China (30972840) to QL, ZJNSF (Z2101211), QL, WZKJ (Y20100046) BW, and the


ZJNSF (D2080515) to WZ. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Anesthesiology of the 2nd Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical


College, Wenzhou, 325000, China Bo Yang, Ben-fu Wang, Xiao-wei Yang & Qing-quan Lian * Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo,


315010, China Miao-jun Lai, Fu-qiang Zhang & Wen-hua Zhou Authors * Bo Yang View author publications You can also search for this author inPubMed Google Scholar * Ben-fu Wang View author


publications You can also search for this author inPubMed Google Scholar * Miao-jun Lai View author publications You can also search for this author inPubMed Google Scholar * Fu-qiang Zhang


View author publications You can also search for this author inPubMed Google Scholar * Xiao-wei Yang View author publications You can also search for this author inPubMed Google Scholar *


Wen-hua Zhou View author publications You can also search for this author inPubMed Google Scholar * Qing-quan Lian View author publications You can also search for this author inPubMed 


Google Scholar CORRESPONDING AUTHORS Correspondence to Wen-hua Zhou or Qing-quan Lian. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yang, B., Wang,


Bf., Lai, Mj. _et al._ Differential involvement of GABAA and GABAB receptors in propofol self-administration in rats. _Acta Pharmacol Sin_ 32, 1460–1465 (2011).


https://doi.org/10.1038/aps.2011.123 Download citation * Received: 20 March 2011 * Accepted: 08 August 2011 * Published: 10 October 2011 * Issue Date: December 2011 * DOI:


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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * addiction * propofol * drug abuse * GABA receptors *


baclofen * bicuculline * ventral tegmental area (VTA) * locomotor activity