Neuroadaptive effects of active versus passive drug administration in addiction research

Jacobs, Edwin H.; Smit, August B.; Vries, Taco J. De; Schoffelmeer, Anton N. M.

doi:10.1016/j.tips.2003.09.006

Cited by 148 publications

(127 citation statements)

References 49 publications

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“…First, acquisition of cocaine CPP was obtained with involuntary cocaine administration rather than selfadministration. It is well established that the behavioral and neurochemical effects of voluntary vs involuntary cocaine administration differ (eg Hemby et al, 1997;Jacobs et al, 2003;Wise, 2000). Moreover, the duration and amount of cocaine exposure in the self-administering rats of the present study was considerably greater compared to that in the CPP studies.…”

Section: Discussionmentioning

confidence: 57%

Differential Effects of σ1 Receptor Blockade on Self-Administration and Conditioned Reinstatement Motivated by Cocaine vs Natural Reward

Martin‐Fardon

Maurice

Aujla

et al. 2007

Neuropsychopharmacol

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Growing evidence suggests a role for sigma 1 (s 1 ) receptors in cognitive function, anxiety, depression, regulation of stress responses, and, recently, the appetitive effects of cocaine as measured by conditioned place preference. This study was designed to extend understanding of the role of s 1 receptors in addiction-relevant conditioned effects of cocaine by testing the effects of a potent and selective s 1 receptor antagonist, BD1047, on conditioned reinstatement of cocaine-seeking. To determine whether modification of conditioned reinstatement by BD1047 is selective for drug-directed behavior or reflects general suppressant effects on motivated behavior, BD1047 was tested also on reinstatement induced by stimuli conditioned to a natural reward, sweetened condensed milk (SCM). Additionally, because s 1 receptors have been implicated also in processes linked to the acute reinforcing actions of cocaine, tests of the effects of BD1047 on cocaine self-administrationFincluding a comparison with the s 1 antagonist effects on SCM self-administrationFwere conducted as well. Cocaine self-administering male Wistar rats were trained to associate a discriminative stimulus (S D ) with the availability of cocaine or SCM, and then subjected to reinstatement tests following extinction of cocaine or SCM-reinforced behavior. BD1047 (1-30 mg/kg) reversed response reinstatement induced by the cocaine S D at 20 and 30 mg/kg but did not modify SCM S D -induced responding at all but the highest 30 mg dose, at which responding was reversed to extinction levels. BD1047 did not modify responding reinforced directly by SCM or cocaine. The findings support a role for s 1 receptors in regulating conditioned responses to cocaine-related contextual stimuli and identify this receptor as a potential treatment target for the prevention of craving and relapse.

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Section: Discussionmentioning

confidence: 57%

Differential Effects of σ1 Receptor Blockade on Self-Administration and Conditioned Reinstatement Motivated by Cocaine vs Natural Reward

Martin‐Fardon

Maurice

Aujla

et al. 2007

Neuropsychopharmacol

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“…It is appreciated that operantly and classically-conditioned behaviors rely upon different but interconnected sets of neural circuits (Berridge and Robinson, 2003), and significantly different effects of contingent versus non-contingent exposure to drugs of abuse on individual elements of those circuits have been well-documented (Jacobs et al, 2003). It is likely that gestational exposure to drugs of abuse, which from the fetal perspective is always behaviorally noncontingent, may affect discrete elements of these developing neural systems at a cellular level in a manner that may result in different or even opposite changes in learned behaviors later in development.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to cocaine alters the development of conditioned place-preference to cocaine in adult mice

Malanga

Pejchal

Kosofsky

2007

Pharmacology Biochemistry and Behavior

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As addiction is increasingly formulated as a developmental disorder, identifying how early developmental exposures influence later responses to drugs of abuse is important to our understanding of substance abuse neurobiology. We have previously identified behavioral changes in adult mice following gestational exposure to cocaine that differ when assessed with methods employing contingent and non-contingent drug administration. We sought to clarify this distinction using a Pavlovian behavioral measure, conditioned place-preference. Adult mice exposed to cocaine in utero (40 or 20 mg/kg/day), vehicle and pair-fed controls were place-conditioned to either cocaine (5 mg/kg or 20 mg/kg, i.p.) or saline injections. The development of conditioned place-preference to cocaine was impaired in mice exposed to cocaine in utero, and was abolished by fetal malnutrition. A context-specific place-aversion to vehicle but not cocaine injection was observed in prenatally cocaine-exposed mice. Locomotor behavior did not differ among prenatal treatment groups. We conclude that early developmental exposure to cocaine may diminish the subsequent rewarding effects of cocaine in adulthood measured with classical conditioning techniques, and that this is not due to changes in locomotor behavior. Sensitivity to acute stress is also altered by prenatal cocaine exposure, consistent with earlier findings in this model.

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“…The reinforcing qualities of the drug are gauged by varying the number of responses required to obtain a drug dose. The more responses an animal provides to obtain a drug, the more reinforcing the drug (Gardner, 2000;Jacobs et al, 2003). Fixed ratio (FR) models of reinforcement are often used to assess drug effects.…”

Section: Overview Of Animal Models Of Addictionmentioning

confidence: 99%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

157

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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Neuroadaptive effects of active versus passive drug administration in addiction research

Cited by 148 publications

References 49 publications

Differential Effects of σ1 Receptor Blockade on Self-Administration and Conditioned Reinstatement Motivated by Cocaine vs Natural Reward

Differential Effects of σ1 Receptor Blockade on Self-Administration and Conditioned Reinstatement Motivated by Cocaine vs Natural Reward

Prenatal exposure to cocaine alters the development of conditioned place-preference to cocaine in adult mice

The Role of Acetylcholine in Cocaine Addiction

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