Conditioned Locomotion Is Not Correlated with Behavioral Sensitization to Cocaine An Intra-Laboratory Multi-Sample Analysis

Hotsenpiller, Gregory; Wolf, Marina E.

doi:10.1016/s0893-133x(02)00370-6

Cited by 23 publications

(12 citation statements)

References 32 publications

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“…It is not surprising that this was observed for nonsensitized as well as sensitized rats, because all cocaine-treated rats, regardless of whether they ultimately sensitize or not, respond to each cocaine injection in the test environment with enhanced locomotor activity and therefore learn similar associations between cocaine and the test environment. There was no significant correlation between the magnitude of behavioral sensitization (day 7/day 1 or withdrawal day 14/day 1 ratios) and conditioned locomotion for individual rats (data not shown), consistent with our previous report (Hotsenpiller and Wolf, 2002).…”

Section: Assessment Of Behavioral Sensitizationsupporting

confidence: 92%

Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases

Boudreau¹,

Reimers²,

Milovanovic³

et al. 2007

J. Neurosci.

251

399

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Although some studies report increased responsiveness of nucleus accumbens (NAc) AMPA receptors (AMPARs) after withdrawal from repeated cocaine treatment, others report decreased responsiveness after withdrawal plus cocaine challenge. Here we examine this apparent contradiction by quantifying cell surface and intracellular AMPAR subunits in the NAc before and after a challenge injection in behaviorally sensitized rats. Because MAPKs (mitogen-activated protein kinases) regulate AMPAR trafficking and are implicated in addiction, we also evaluated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Glutamate receptor 1 (GluR1) and GluR2 surface/intracellular (S/I) ratios were increased after 14 d of withdrawal in sensitized rats but were decreased 24 h after challenge with cocaine (which elicited a sensitized locomotor response) or saline (which elicited conditioned locomotion). These findings suggested redistribution of GluR1/2-containing receptors, a possibility supported by immunoprecipitation experiments indicating that most AMPARs in the NAc are GluR1/2 or GluR2/3, with few homomeric GluR1 or GluR1/3 receptors. In sensitized rats, ERK phosphorylation in the NAc increased during withdrawal and normalized after cocaine challenge. JNK phosphorylation also increased after withdrawal, but after cocaine challenge, it was inversely related to GluR1 and GluR2 S/I ratios. After saline challenge, p38 phosphorylation was increased. In summary, surface expression of GluR1/2-containing AMPARs increased in the NAc of sensitized rats, but AMPARs internalized after a single reexposure to cocaine or cocaine-related cues. ERK phosphorylation paralleled AMPAR surface expression. Although JNK results were complex, JNK and p38 may be involved in AMPAR internalization after cocaine or saline challenge, respectively.

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Section: Assessment Of Behavioral Sensitizationsupporting

confidence: 92%

Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases

Boudreau¹,

Reimers²,

Milovanovic³

et al. 2007

J. Neurosci.

251

399

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“…Independently of the ability to potentiate the behavioral sensitization phenomenon, these conditioned responses are per se considered animal models to study addiction (Damianopoulos and Carey, 1992;Carey and Damianopoulos, 1994;Hotsenpiller et al, 2002;Hotsenpiller and Wolf, 2002a). Within this context, it has been shown that conditioned locomotion is not directly correlated to behavioral sensitization to psychostimulants (Carey and Gui, 1998;Hotsenpiller et al, 2001;Hotsenpiller and Wolf, 2002b).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Rapid-Onset Type of Behavioral Sensitization to Amphetamine in Mice: Role of Drug–Environment Conditioning

Chinen

Faria

Frussa‐Filho

2005

Neuropsychopharmacol

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A rapid-onset type of behavioral sensitization (ROBS) has been demonstrated in rats treated with a single 'priming' injection of amphetamine (AMP). In that species, however, this phenomenon was restricted to AMP-induced stereotyped behavior (SB), not occurring for the locomotor-stimulant effect (LSE) of AMP and not reflecting environment-specific sensitization. In the present study, the ROBS was characterized in the mouse. Mice received a single 'priming' intraperitoneal injection of 5.0 mg/kg AMP which was paired or not with environment. At different intervals (3, 4 or 5 h) subgroups were tested for AMP (1.5 or 5.0 mg/kg)-induced SB or AMP (1.5 mg/kg)-induced open-field LSE. Results showed that: (1) in the absence of drug-environment association, a priming injection of AMP increased the SB induced by a 1.5 mg/kg AMP challenge injection given 3 h (but not 4 or 5 h) later; (2) when the dose of AMP challenge injection was increased to 5.0 mg/kg, an enhancement of SB was verified at all the intervals tested (3, 4, and 5 h); (3) when animals were tested in an open field, the priming injection of AMP produced an increase in the LSE of a 1.5 mg/kg AMP challenge injection, given 4 h later; (4) drug-environment association increased both SB and locomotion after a saline challenge injection and potentiated the rapid-onset sensitization of both behaviors in AMP-challenged mice. Collectively, these results demonstrate that the ROBS phenomenon also occurs in mice, is extended to AMP-induced LSE, and is markedly potentiated by (but does not depend on) environmental conditioning. Neuropsychopharmacology (2006) 31, 151-159.

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“…It has been argued, for example, that behavioral sensitization is context specific because environmental stimuli acquire excitatory CS + properties, producing a progressively increasing conditioned response that adds to the unchanging unconditioned psychomotor drug effect (Tilson and Rech, 1973;Hinson and Poulos, 1981;Pert et al, 1990). This 'simple' excitatory conditioned model of sensitization clearly does not suffice here (Anagnostaras and Robinson, 1996;Martin-Iverson and Fawcett, 1996;Carey and Gui, 1998;Crombag et al, 2000;Hotsenpiller and Wolf, 2002), suggesting that more complex associative-learning processes are involved (Bouton, 1991;Holland, 1992;Anagnostaras and Robinson, 1996).…”

Section: Sensitization Of Psychomotor Activationmentioning

confidence: 99%

Sensitization of Psychomotor Stimulation and Conditioned Reward in Mice: Differential Modulation by Contextual Learning

Mead

Crombag

Rocha

2003

Neuropsychopharmacol

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Incentive motivation theory ascribes a critical role to reward-associated stimuli in the generation and maintenance of goal-directed behavior. Repeated psychomotor stimulant treatment, in addition to producing sensitization to the psychomotor-activating effects, can enhance the incentive salience of reward-associated cues and increase their ability to influence behavior. In the present study, we sought to investigate this incentive sensitization effect further by developing a model of conditioned reinforcement (CR) in the mouse and investigating the effects of a sensitizing treatment regimen of amphetamine on CR. Furthermore, we assessed the role of contextual stimuli in amphetamine-induced potentiation of CR. We found that mice responded selectively on a lever resulting in the presentation of a cue previously associated with 30% condensed milk solution, indicating that the cue had attained rewarding properties. Prior treatment with amphetamine (4 Â 0.5 mg/kg i.p.) resulted in psychomotor sensitization and enhanced subsequent responding for the CR. Furthermore, this enhancement of responding for the cue occurred independent of the drug-paired context, whereas the sensitized locomotor response was only observed when mice were tested in the same environment as that in which they had received previous amphetamine. These results demonstrate that the CR paradigm previously developed in the rat can be successfully adapted for use in the mouse, and suggest that behavioral sensitization to amphetamine increases the rewarding properties (incentive salience) of rewardpaired cues, independent of the drug-paired context.

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Conditioned Locomotion Is Not Correlated with Behavioral Sensitization to Cocaine An Intra-Laboratory Multi-Sample Analysis

Cited by 23 publications

References 32 publications

Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases

Cell Surface AMPA Receptors in the Rat Nucleus Accumbens Increase during Cocaine Withdrawal But Internalize after Cocaine Challenge in Association with Altered Activation of Mitogen-Activated Protein Kinases

Characterization of the Rapid-Onset Type of Behavioral Sensitization to Amphetamine in Mice: Role of Drug–Environment Conditioning

Sensitization of Psychomotor Stimulation and Conditioned Reward in Mice: Differential Modulation by Contextual Learning

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