Chronic flupentixol treatment potentiates the reinforcing properties of systemic heroin administration

Stinus, Luis; Nadaud, D.; Deminière, Jean-Marie; Jauregui, J; Hand, Timothy T.; Moal, Michel Le

doi:10.1016/0006-3223(89)90052-8

Cited by 48 publications

(18 citation statements)

References 25 publications

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“…Thus, the enhanced sensitivity to cocaine seen in the present study may also reflect an augmentation in the positive reinforcing effects of cocaine. This interpretation is supported by a previous study in which longterm exposure to the mixed D 1 /D 2 antagonist, flupenthixol, increased the sensitivity to both the place conditioning and self-administration effects of heroin (Stinus et al 1989).…”

Section: Discussionsupporting

confidence: 63%

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

1996

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Many behavioral effects of cocaine are attenuated by dopamine (DA) receptor antagonists. Yet, long-term DA antagonist administration enhances neuronal responsiveness to DA in several pathways, including the mesolimbic system. This study compared the effects of short-term versus long-term administration of the DA antagonist, haloperidol, on cocaine place conditioning. In the short-term study, rats were maintained on haloperidol or vehicle for the 10 days of place conditioning. Place conditioning to moderate doses of cocaine (10-15 mg/kg) was attenuated significantly, consistent with the dopaminergic actions of haloperidol and cocaine. In the second study, rats were administered haloperidol after place conditioning which had no effect on the expression of this behavior. Finally, rats were maintained on haloperidol for 30 days prior to and throughout place conditioning and testing which resulted in significant place conditioning at low cocaine doses (2.5-7.5 mg/kg). Because these cocaine doses do not support place conditioning in vehicle-maintained rats, these data suggest that long-term haloperidol administration enhances the sensitivity to these behavioral effects in contrast to the attenuation seen with short-term haloperidol administration. These results have wide-ranging implications for cocaine abuse treatment, particularly among schizophrenic populations.

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Section: Discussionsupporting

confidence: 63%

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

1996

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“…1). Finally, chronic blockade of dopamine receptors with a-flupenthixol strongly potentiates, rather than inhibits, the rewarding effect of low heroin doses 255 .…”

Section: Figurementioning

confidence: 98%

Opiate versus psychostimulant addiction: the differences do matter

et al. 2011

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The publication of the psychomotor stimulant theory of addiction in 1987 and the finding that addictive drugs increase dopamine concentrations in the rat mesolimbic system in 1988 have led to a predominance of psychobiological theories that consider addiction to opiates and addiction to psychostimulants as essentially identical phenomena. Indeed, current theories of addiction — hedonic allostasis, incentive sensitization, aberrant learning and frontostriatal dysfunction — all argue for a unitary account of drug addiction. This view is challenged by behavioural, cognitive and neurobiological findings in laboratory animals and humans. Here, we argue that opiate addiction and psychostimulant addiction are behaviourally and neurobiologically distinct and that the differences have important implications for addiction treatment, addiction theories and future research.

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“…The sites of action for opioid antagonists to block the reinforcing effects of opiates appears to be associated with the same neural circuitry associated with psychomotor stimulant reward (Table 1). Much data suggest that neural elements in the region of the ventral tegmental area and the nucleus accumbens are responsible for the reinforcing properties of opiates and that there are both dopamine-dependent and dopamineindependent mechanisms of opiate action (Pettit et al 1984; Shippenberg et al 1992;Spyraki et al 1983;Stinus et al 1989). …”

Section: Opiatesmentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,515

1,962

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This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

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Chronic flupentixol treatment potentiates the reinforcing properties of systemic heroin administration

Cited by 48 publications

References 25 publications

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

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

Opiate versus psychostimulant addiction: the differences do matter

Drug Addiction, Dysregulation of Reward, and Allostasis

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