Pharmacological regulation of intravenous cocaine and heroin self-administration in rats: A variable dose paradigm

Gerber, Gary; Wise, Roy A.

doi:10.1016/0091-3057(89)90192-5

Cited by 111 publications

(100 citation statements)

References 18 publications

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“…determined largely by the duration of the effect of each injection (Gerber and Wise, 1989;Panlilio et al, 2003;Tsibulsky and Norman, 1999), but drug-seeking under progressive-ratio schedules is essentially independent of duration of effect (Panlilio and Schindler, 2000; see also Ko et al, 2002). Thus, cross-tolerance to heroin's locomotorsuppressant effects would be expected to increase heroin intake under the FR1 schedule, but it should not alter the reinforcing efficacy of heroin under the progressive-ratio schedule.…”

Section: Discussionmentioning

confidence: 99%

“…The primary datum was the amount of time between consecutive injections. This latency measure (ie, the inter-injection interval or postinjection pause) typically varies as a direct function of dose, allowing a dose-effect curve to be obtained within a single session (Gerber and Wise, 1989;Panlilio and Schindler, 2000;Solinas et al, 2004). Data were analyzed for the second of the two variable-dose sessions before the progressiveratio phase of Experiment 1 and also for the second of the two variable-dose sessions after the progressive-ratio phase.…”

Section: Subjectsmentioning

confidence: 99%

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Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol (THC) exposure, then allowing them to self-administer other drugs. In Experiment 1, THC preexposure did not alter the acquisition of cocaine self-administration or the amount of cocaine taken under a fixed-ratio 1 (FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine-seeking was significantly reduced in THC-exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive-ratio schedule, but it increased heroin self-administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC-exposed rats under FR1 heroin self-administration. When given cocaine, THCexposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC preexposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effectFwhich was verified in Experiment 3 using another model of anxiety, the light-dark testFmay explain the reduced reinforcing value of cocaine observed in THC-exposed rats in Experiment 1.

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Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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“…These findings were also recently confirmed by Gál and Gyertyán [102] who showed that acute administration of SB-277011-A (5 and 20 mg/kg po) does not affect cocaine self-administration under continuous reinforcement. In contrast, the same study showed that both the DA D 1 receptor antagonist SCH-23390 (0.1 and 0.2 mg/kg ip) and the DA D 2 -preferring receptor antagonist haloperidol (0.2 and 0.5 mg/kg po) produced a compensatory increase in lever pressing, of the type classically known to be produced by DA antagonists [110,311]. Finally, the mixed D 2 /D 3 agonists PD-128907 (1 mg/kg sc) and 7-OH-DPAT (0.1 and 0.5 mg/kg sc) produced a significant decrease in lever pressing for cocaine.…”

Section: Effect Of Sb-277011-a On Cocaine Self-administration and Cocmentioning

confidence: 93%

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

305

249

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The cDNA for the dopamine D 3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D 3 receptors, as well as D 3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D 3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D 3 receptors. The interpretation of results from studies using mixed D 2 /D 3 agonists and/or antagonists is problematic because these agents have low selectivity for D 3 over D 2 receptors and it is likely that their actions are primarily related to D 2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D 3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D 3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D 3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D 3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stressinduced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D 3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction.

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“…For example, while 6-OHDA lesions do impair the acquisition of heroin SA (Singer and Wallace, 1984) and decrease morphine SA (Smith et al, 1985) in some studies, these results are not always replicated (Pettit et al, 1984;Dworkin et al, 1988, Gerrits andVan Ree, 1996). In addition, DA receptor antagonism does not consistently alter opiate SA behavior (Ettenberg et al, 1982;Van Ree and Ramsey, 1987;Gerber and Wise, 1989;Gerrits et al, 1994).…”

Section: Ne and Opiate Samentioning

confidence: 98%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

323

277

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Fueled by anatomical, electrophysiological, and pharmacological analyses of endogenous brain reward systems, norepinephrine (NE) was identified as a key mediator of both natural and drug-induced reward in the late 1960s and early 1970s. However, reward experiments from the mid-1970s that could distinguish between the noradrenergic and dopaminergic systems resulted in the prevailing view that dopamine (DA) was the primary 'reward transmitter' (a belief holding some sway still today), thereby pushing NE into the background. Most damaging to the NE hypothesis of reward were studies demonstrating that NE receptor antagonists and NE reuptake inhibitors failed to impact drug self-administration. In recent years new tools, such as genetically engineered mice, and new experimental paradigms, such as reinstatement of drug seeking following withdrawal, have propelled NE back into the awareness of addiction researchers. Of particular interest is disulfiram, an inhibitor of the NE biosynthetic enzyme dopamine b-hydroxylase, which has demonstrated promising efficacy in the treatment of cocaine dependence in preliminary clinical trials. The purpose of this review is to synthesize the new data linking NE to critical aspects of DA signaling and drug addiction, with a focus on psychostimulants (eg, cocaine), opiates (eg, morphine), and alcohol.

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Pharmacological regulation of intravenous cocaine and heroin self-administration in rats: A variable dose paradigm

Cited by 111 publications

References 18 publications

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

There and Back Again: A Tale of Norepinephrine and Drug Addiction

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