Principles of drug abuse liability assessment in laboratory animals

Ator, Nancy A.; Griffiths, Roland R.

doi:10.1016/s0376-8716(03)00099-1

Cited by 232 publications

(188 citation statements)

References 81 publications

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“…Multiple behavioral assays can be used to index abuse potential [1][2][3] including the capacity of a drug to induce hyperlocomotion [4] and the capacity to induce conditioned place preference [5]. Rats will self-administer drugs such as cocaine or amphetamine into their vascular system [6].…”

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confidence: 99%

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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The alkaloid lobeline inhibits the function of vesicular monoamine and dopamine transporters and diminishes the behavioral and neurochemical effects of nicotine and amphetamines. In the present study, we examined the interaction of systemic administration of lobeline on breakpoint scores on a progressive ratio (PR) schedule of intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). Rats were run in two 30 min sessions, separated by a 10 min timeout period. At the end of the first session, each rat was injected with either 0, 0.5, 1.0 or 2.0 mg/kg (i.p.) lobeline. Positive controls known to suppress and to augment ICSS responding included the adrenergic antagonist prazosin (0, 0.5 and 2.0 mg/kg, i.p.) and the psychostimulant cocaine (0, 1.25, and 5.0 mg/kg, i.p.). Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR scores at doses of 0.5, 1.0 and 2.0 mg/kg, as did 0.5 mg/kg and 2.0 mg/ kg prazosin. These changes are unlikely to reflect motoric effects of these drugs inasmuch as neither lobeline nor prazosin alter locomotion at these doses. In contrast, PR breakpoint scores were significantly increased at 5.0 mg/kg cocaine, a dose that is sufficient to elevate locomotion in the rat. These results are consistent with the view that lobeline modulates brain reinforcement processes. Keywords Nicotinic receptors; Prazosin; CocaineMultiple behavioral assays can be used to index abuse potential [1][2][3] including the capacity of a drug to induce hyperlocomotion [4] and the capacity to induce conditioned place preference [5]. Rats will self-administer drugs such as cocaine or amphetamine into their vascular system [6]. Such drug infusions are thought to act on the neural substrates of reward. Electrodes placed along the path of the medial forebrain bundle (MFB) will support intracranial self-stimulation (ICSS) [7] and drugs of abuse are known to reduce the threshold current required to support ICSS [4,8,9]. Additionally, drugs of abuse are known to elevate progressive ratio (PR) responding for ICSS [10,11]. The latter types of studies are important in that a PR schedule, relative to a continuous reinforcement schedule, may be more sensitive to changes in reward engendered by neurotransmitter receptor antagonism [12].The alkaloid lobeline is derived from lobelia inflata [13]. Lobeline attenuates the hyperactivity induced by methamphetamine in rats and diminishes methamphetamine self-administration in rats [14][15][16]. The aforementioned results suggest that lobeline may function as a therapeutic tool for the treatment of methamphetamine abuse. Inasmuch as the impact of lobeline on ICSS responding has not been previously reported, the present study considered the impact of lobeline on breakpoints on a PR schedule of ICSS reinforcement. In this paradigm, the response requirement for reinforcement is increased systematically within a 30 min session [17]. Following completion of the first session, each rat was injected (i.p.)...

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mentioning

confidence: 99%

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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“…It means, among other aspects, that long-term effects of cocaine consumption may be more easily modeled for a specific developmental stage, such as adolescence. It also allows studies of a drug's cumulative effects or cross-drug comparisons in the same subject (Ator & Griffiths, 2003). Together with their greater physiological similarities and behavioral diversity, longevity makes NHP models key for addiction research.…”

Section: The Case For Non-human Primates As Modelsmentioning

confidence: 99%

“…There is rather a powerful tool in primate research that allows for a greater and more refined analysis of the intricacies of cocaine effects: primate behavior. In this sense, one of the most widespread and reliable tests for cocaine addiction is the selfadministration paradigm (Griffiths et al, 1980;Ator & Griffiths, 2003). In this model, the animal subject is trained to press a lever or push a button to receive a rewarding stimulus (e.g.…”

Section: The Case For Non-human Primates As Modelsmentioning

confidence: 99%

“…The extensive amount of rodent research also spurs a faster refinement of the techniques, which in turn, makes rodents an even more practical and useful model. In terms of cocaine addiction, rats have been employed in several paradigms (self-administration, conditioned place-preference, open field; Mello & Negus, 1996;Ator & Griffiths, 2003) and also make up the majority of cocaine-related studies. Unfortunately, there is a significant genetic gap between humans and rodents: the actual figure being 66-82% homology (Nilsson et al, 2001).…”

Section: The Case For Non-human Primates As Modelsmentioning

confidence: 99%

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Contributions of Non-Human Primates to the Understanding of Cocaine Addiction

Maior¹,

Barros²,

Tomaz³

2011

Psychiatric Disorders - Trends and Developments

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“…13 Manipulating the number of lever presses necessary for an animal to self-administer drug helps evaluate the reinforcing effects of a drug or other reward. For example, a "fixed ratio" schedule of drug administration (e.g., every five lever presses results in the delivery of one dose) will result in a drug-specific operant response pattern; whereas a "progressive ratio" schedule (e.g., each subsequent drug delivery follows a numerical progression of required lever presses such as 1, 2, 4, 8, 16, 32…) will result in a very different pattern depending on how intensely the animal wants the next dose of that drug.…”

Section: Studying Self-administration Of Drugsmentioning

confidence: 99%

L’analgésie contrôlée avec patience: vers une meilleure compréhension des comportements d’auto-administration des analgésiques

Gilron

2008

Can J Anesth/J Can Anesth

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Principles of drug abuse liability assessment in laboratory animals

Cited by 232 publications

References 81 publications

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Contributions of Non-Human Primates to the Understanding of Cocaine Addiction

L’analgésie contrôlée avec patience: vers une meilleure compréhension des comportements d’auto-administration des analgésiques

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