Intravenous Scopolamine Is Potently Self-Administered in Drug-Naive Mice

Rasmussen, Torben Valdbjørn; Fink-Jensen, Anders

doi:10.1016/s0893-133x(99)00088-3

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…In general, these studies found that ICSS was depressed by mAChR agonists (arecoline and pilocarpine) and the AChE inhibitor physostigmine, but facilitated by the mAChR antagonist scopolamine (Olds and Domino, 1969;Olds, 1972;Druhan et al, 1989). The facilitation of ICSS by scopolamine parallels evidence for reinforcing effects of scopolamine in drug self-administration procedures in rats and mice (Glick and Guido, 1982;Rasmussen and Fink-Jensen, 2000). Other studies have examined effects of centrally administered mAChR ligands, and in contrast to effects of systemic administration, both scopolamine and the other mAChR antagonist atropine depressed ICSS (Kofman and Yeomans, 1988).…”

Section: Cholinergic Drugsmentioning

confidence: 83%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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Section: Cholinergic Drugsmentioning

confidence: 83%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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“…In addition, our failure to detect changes in performance on saline injection days between atropine exposures suggest that such effects were small at best, but such effects cannot be rule out. However, it is not unusual to observe an inverted U-shaped function of learning or performance effects with muscarinic anticholinergic drugs such as atropine and scopolamine (e.g., Carnicella et al, 2005a, 2005b; Rasmussen & Fink-Jensen, 2000; Stewart & Blain, 1975), and such effects have been attributed to drug effects on cortical arousal measured by EEG and concomitant cognitive arousal that align with the Yerkes-Dodson law (Graef, Schoknecht, Sabri, & Hegerl, 2011). …”

Section: Discussionmentioning

confidence: 99%

Central cholinergic involvement in sequential behavior: Impairments of performance by atropine in a serial multiple choice task for rats

Fountain

Rowan

Wollan

2013

Neurobiology of Learning and Memory

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Two experiments examined whether muscarinic cholinergic systems play a role in rats’ ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats’ performance on pattern elements learned by encoding rules versus by acquisition of stimulus-response (S-R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats’ ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent “violation elements” and elements following “phrasing cues,” where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S-R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood-brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S-R associations were important for performance, namely, chunk-boundary elements. However, in the structurally more ambiguous unphrased perfect pattern where rats had fewer cues and presumably relied more on S-R associations throughout, atropine impaired performance on all pattern elements. Thus, intact muscarinic cholinergic systems were shown to be necessary for discriminative control previously established by S-R learning, but were not necessary for rule-based serial pattern performance.

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“…Recently, studies have been published by several groups employing an acute mouse model where animals are tested in pairs using a contingent and a yoked control mouse, which enables rapid assessment of the reinforcing properties of a compound. Although this acute model is thought to assess the initiation rather than the chronic maintenance of drug-taking behavior, it was demonstrated that drug-naïve mice acutely self-administer the same drugs that humans abuse, such as cocaine (Kuzmin et al, 1992; Kuzmin et al, 1996c; Kuzmin et al, 1996d; Kuzmin and Johansson, 2000; Kuzmin et al, 2000; Rasmussen et al, 2000; Blokhina et al, 2005; Lesscher et al, 2005), morphine (Kuzmin et al, 1996a; Kuzmin et al, 1997), amphetamine (Cossu et al, 2001), cannabinoids (Martellotta et al, 1998a), γ-hydroxybutyric acid (Martellotta et al, 1998c; Fattore et al, 2000; Fattore et al, 2001), scopolamine (Rasmussen and Fink-Jensen, 2000), and nicotine (Martellotta et al, 1995; Rasmussen and Swedberg, 1998; Fattore et al, 2002; Paterson et al, 2003). These studies demonstrated that drug-naïve mice exhibit SA behavior similar to rats chronically trained under the same schedule of reinforcement (FR1) and using the same operant response, i.e.…”

Section: Introductionmentioning

confidence: 99%

Crucial Role of α4 and α6 Nicotinic Acetylcholine Receptor Subunits from Ventral Tegmental Area in Systemic Nicotine Self-Administration

Pons¹,

Fattore²,

Cossu³

et al. 2008

J. Neurosci.

305

395

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The identification of the molecular mechanisms involved in nicotine addiction and its cognitive consequences is a worldwide priority for public health. Novel in vivo paradigms were developed to match this aim. Although the ␤2 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) has been shown to play a crucial role in mediating the reinforcement properties of nicotine, little is known about the contribution of the different ␣ subunit partners of ␤2 (i.e., ␣4 and ␣6), the homo-pentameric ␣7, and the brain areas other than the ventral tegmental area (VTA) involved in nicotine reinforcement. In this study, nicotine (8.7-52.6 g free base/kg/inf) selfadministration was investigated with drug-naive mice deleted (KO) for the ␤2, ␣4, ␣6 and ␣7 subunit genes, their wild-type (WT) controls, and KO mice in which the corresponding nAChR subunit was selectively re-expressed using a lentiviral vector (VEC mice). We show that WT mice, ␤2-VEC mice with the ␤2 subunit re-expressed exclusively in the VTA, ␣4-VEC mice with selective ␣4 re-expression in the VTA, ␣6-VEC mice with selective ␣6 re-expression in the VTA, and ␣7-KO mice promptly self-administer nicotine intravenously, whereas ␤2-KO, ␤2-VEC in the substantia nigra, ␣4-KO and ␣6-KO mice do not respond to nicotine. We thus define the necessary and sufficient role of ␣4␤2-and ␣6␤2-subunit containing nicotinic receptors (␣4␤2*-and ␣6␤2*-nAChRs), but not ␣7*-nAChRs, present in cell bodies of the VTA, and their axons, for systemic nicotine reinforcement in drug-naive mice.

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Intravenous Scopolamine Is Potently Self-Administered in Drug-Naive Mice

Cited by 12 publications

References 17 publications

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

Central cholinergic involvement in sequential behavior: Impairments of performance by atropine in a serial multiple choice task for rats

Crucial Role of α4 and α6 Nicotinic Acetylcholine Receptor Subunits from Ventral Tegmental Area in Systemic Nicotine Self-Administration

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