Sensitization and Tolerance in Psychostimulant Self-Administration

Schenk, Susan; Partridge, Brian

doi:10.1016/s0091-3057(96)00447-9

Cited by 114 publications

(69 citation statements)

References 32 publications

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“…In the literature, adult rats pretreated with psychostimulants have been shown to acquire cocaine selfadministration more rapidly [27,42] and have higher rates of responding [40] than rats pretreated with saline. This decrease in latency to acquire self-administration has been interpreted to indicate that cocaine pre-exposure sensitizes the rats to the reinforcing effects of cocaine [41]. In our study, nicotine-pretreated adolescent animals showed a similar pattern of enhanced responding.…”

Section: Discussionsupporting

confidence: 72%

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

McQuown

Belluzzi

Leslie

2007

Neurotoxicology and Teratology

100

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Adolescence is a critical period for the initiation of drug use, starting with tobacco and alcohol and progressing to marijuana and other illicit drugs. These findings have led to the suggestion that tobacco and alcohol are 'gateway' drugs that sensitize maturing reward pathways to the effects of illicit substances such as cocaine. To test this hypothesis, we have examined whether low-dose nicotine pretreatment alters acquisition of cocaine self-administration in adolescents more than in adults. Male and female Sprague-Dawley rats, aged postnatal day (P) 28 or P86, were given two daily intravenous injections of nicotine (0.03 mg/kg/0.1 ml) or saline for four days. At P32 and P90, rats were placed in self-administration chambers and tested for acquisition of cocaine (0.2 or 0.5 mg/kg/inj) for five days. Data were collapsed across cocaine dose and sex since there was no significant effect of these variables. Adolescent rats pretreated with nicotine exhibited significantly greater cocaine-reinforced responding as compared to saline controls or adults (p < 0.01). This drug pretreatment effect did not generalize to all rewards, since nicotine did not increase responding for sucrose pellets in adolescents. These findings provide evidence that the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

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Section: Discussionsupporting

confidence: 72%

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

McQuown

Belluzzi

Leslie

2007

Neurotoxicology and Teratology

100

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“…Therefore, the data suggest that the dose-response function of cocaine was shifted upward as session duration increased. An upward shift of a psychostimulant dose-response function was also found in rats and rhesus monkeys after chronic self-administration/ administration of the drugs (Woolverton et al, 1984;Schenk and Partridge, 1997;Mantsch et al, 2004).…”

Section: Discussionmentioning

confidence: 65%

Effects of Dose and Session Duration on Cocaine Self-Administration in Rats

Wee

Specio²,

Koob³

2007

The Journal of Pharmacology and Experimental Therapeutics

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Previous studies showed that an extended 6-h session duration produced an increasing rate of cocaine self-administration in rats. The present study further investigated the effect of dose and session duration on cocaine self-administration. Eight groups of rats (4 doses ϫ 2 session durations) self-administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/ injection) in either 1-or 6-h sessions under a fixed-ratio schedule. In another experiment, two other groups of rats selfadministered 0.5 mg/kg/injection of cocaine in either 3-or 12-h sessions. Cocaine self-administration increased at all doses in 6-h sessions but not in 1-h sessions. Cocaine intake (milligram/ kilogram) reached an asymptote earlier at a higher dose, but the rate of responding increased faster when the dose was lower.

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“…With sensitization, empirical data support the hypothesis that the locomotor-activating effects (psychomotor sensitization) of many drugs of abuse show sensitization with repeated administration of nondependenceinducing doses (e.g., doses that do not induce physical signs of withdrawal upon abstinence). This psychomotor sensitization has been extended with certain drugs under certain situations to the reinforcing effects of drugs (Schenk and Partridge 1997) where animals with a history of drug administration initiate drug selfadministration at lower doses than drug-naive subjects. Thus, a history of drug intake could shift the dose-effect function to the left to initiate drug-seeking behavior, increase self-administration at low doses that do not normally sustain self-administration, and produce a larger neurobiological effect in an experienced subject than if given to a drug-naive subject.…”

Section: Allostasis and Neuroadaptationmentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,564

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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Sensitization and Tolerance in Psychostimulant Self-Administration

Cited by 114 publications

References 32 publications

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

Effects of Dose and Session Duration on Cocaine Self-Administration in Rats

Drug Addiction, Dysregulation of Reward, and Allostasis

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