Long-term haloperidol administration enhances and short-term administration attenuates the behavioral effects of cocaine in a place conditioning procedure

Kosten, Therese A.; DeCaprio, Jenine L; Nestler, Eric J.

doi:10.1007/s002130050138

Cited by 35 publications

(26 citation statements)

References 44 publications

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“…Although acute administration of dopamine D1 or D2 antagonists can block cocaine's reinforcing and discriminative-stimulus effects, repeated antagonist administration can increase cocaine's reinforcing (self-administration) and rewarding (conditioned place preference) effects in rats (Emmett-Oglesby and Mathis 1988; Kosten et al 1996;Kosten 1997).…”

Section: Rodents and Non-human Primatesmentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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Section: Rodents and Non-human Primatesmentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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“…Animal studies have suggested that repeated exposure to many psychiatric medications alters the density of neurotransmitter receptors, including several receptors implicated in the response to cocaine. Longterm exposure to haloperidol alters the behavioral response of rats to cocaine [99,100]. Furthermore, a recent study reported that long-term ziprasidone increased cocaine toxicity [101].…”

Section: Cocaine Toxicity: Tying Together Concentrations and Receptormentioning

confidence: 99%

Mechanisms of Acute Cocaine Toxicity

Heard¹,

Palmer²,

Zahniser³

2008

TOPHARMJ

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Abstract:Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporter, neurotransmitter receptor and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine and the effects that these interactions trigger. We also describe the progression of symptoms observed in cocaine poisoning as they relate to serum cocaine concentrations.

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“…Haloperidol and clozapine were administered at target doses of 1.8 and 35-40 mg/kg/day, respectively, as used previously (Fitzgerald et al, 1995). This treatment method has been shown to produce consistent and clinically relevant plasma levels of these drugs (Kosten and Nestler, 1994;Fitzgerald et al, 1995;Kosten et al, 1996). In one experiment, haloperidol treatment was continued, at a target dose of 1.5 mg/kg/day, for a total of 24 weeks.…”

Section: Drug Administrationmentioning

confidence: 99%

Region-specific induction of ?FosB by repeated administration of typical versus atypical antipsychotic drugs

Atkins

Chlan-Fourney

Nye

et al. 1999

Synapse

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Whereas acute administration of many types of stimuli induces c-Fos and related proteins in brain, recent work has shown that chronic perturbations cause the region-specific accumulation of novel Fos-like proteins of 35-37 kD. These proteins, termed chronic FRAs (Fos-related antigens), have recently been shown to be isoforms of DeltaFosB, which accumulate in brain due to their enhanced stability. In the present study, we sought to extend earlier findings that documented the effects of acute administration of antipsychotic drugs (APDs) on induction of Fos-like proteins by investigating the ability of typical and aytpical APDs, after chronic administration, to induce these DeltaFosB isoforms in several brain regions implicated in the clinical actions of these agents. By Western blotting we found that chronic administration of the typical APD, haloperidol, dramatically induces DeltaFosB in caudate-putamen (CP), a brain region associated with the extrapyramidal side effects of this drug. A smaller induction was seen in the nucleus accumbens (NAc) and prefrontal cortex (PFC), brain regions associated with the antipsychotic effects of the drug. In contrast, chronic administration of the prototype atypical APD clozapine failed to significantly increase levels of DeltaFosB in any of the three brain regions, and even tended to reduce DeltaFosB levels in the NAc. Two putative atypical APDs, risperidone and olanzapine, produced small but still significant increases in the levels of DeltaFosB in CP, but not NAc or PFC. Studies with selective receptor antagonists suggested that induction of DeltaFosB in CP and NAc is most dependent on antagonism of D2-D3 dopamine receptors, with antagonism of D1-like receptors most involved in the PFC. Immunohistochemical analysis confirmed the greater induction of DeltaFosB in CP by typical versus atypical APDs, with no significant induction seen in PFC with either class of APD. Together, these findings demonstrate that repeated administration of APDs results in the induction of long-lasting Fos-like transcription factors that could mediate some of the persistent and region-specific changes in brain function associated with chronic drug exposure. Synapse 33:118-128, 1999.

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Long-term haloperidol administration enhances and short-term administration attenuates the behavioral effects of cocaine in a place conditioning procedure

Cited by 35 publications

References 44 publications

Controversies in translational research: drug self-administration

Controversies in translational research: drug self-administration

Mechanisms of Acute Cocaine Toxicity

Region-specific induction of ?FosB by repeated administration of typical versus atypical antipsychotic drugs

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