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Stereotyped and complex motor routines expressed during cocaine self-administration: results from a 24-h binge of unlimited cocaine access in rats

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Abstract

Rationale

Cocaine binges represent the most severe form of cocaine taking due to high levels of cocaine consumed and a potential loss of self-control over cocaine taking. Experimentally, regulation of intravenous cocaine self-administration is observed during binges as revealed by nearly constant sequential inter-infusion intervals, suggesting that pharmacological and unconditioned behavioral effects of cumulative cocaine leave intact its reinforcing effect.

Objective

To elucidate factors that contribute to the patterning of cocaine self-administration behavior during binges, the current study quantifies the expression of specific motor routines that emerge from the beginning of a cocaine infusion until the next cocaine reinforcement is received, in six separate rats over 24 h of continuous access.

Materials and methods

During each 24-h cocaine binge, behavior was continuously monitored using a force plate actometer that provides reliable quantitation of rodent behaviors, including rotational behavior, locomotor activity, and focused stereotypy.

Results

Corroborating earlier results, each rat accumulated between 4 and 11 mg/kg/h during periods of active cocaine self-administration. All rats displayed a similar narrow range of unconditioned behavioral responses to cocaine, yet each rat varied with regard to the intensity and specific predominant pattern of behavioral activation. Focused stereotyped behavior, in particular, was apparent in all rats and continued for as long as cocaine self-administration behavior remained active.

Conclusions

The current results support the hypothesis that individual differences in cocaine’s pharmacodynamics may contribute to specific behaviors expressed during cocaine self-administration, but leave unresolved whether or not intense unconditioned behavior (e.g., focused stereotypy) conflicts with, or contributes to, ongoing self-administration behavior.

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References

  • Barbieri EJ, Ferko AP, DiGregorio GJ, Ruch EK (1992) The presence of cocaine and benzylecognine in rat cerebrospinal fluid after the intravenous administration of cocaine. Life Sci 51:1739–1746

    Article  PubMed  CAS  Google Scholar 

  • Bari AA, Pierce RC (2005) D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement. Neuroscience 135:959–968

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Whishaw IQ (1992) Cortex, striatum and cerebellum: control of serial order in a grooming sequence. Exp Brain Res 90:275–290

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Miczek KA (2005) Intense cocaine self administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology 183:331–340

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Kikusui T, Goodhue J, Nikulina EM, Hammer RP Jr, Miczek KA (2005) Brief social defeat stress: long lasting effects on cocaine taking during a binge and zif268 mRNA expression in the amygdala and prefrontal cortex. Neuropsychopharmacology 30:310–321

    Article  PubMed  CAS  Google Scholar 

  • Ellinwood EH, Kilbey MM (1975) Amphetamine stereotypy: the influence of environmental factors and prepotent behavioral patterns on its topography and development. Biol Psychiatry 10:3–16

    PubMed  Google Scholar 

  • Ernst AM (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10:316–323

    Article  PubMed  CAS  Google Scholar 

  • Fowler SC, McKerchar TL, Zarcone TJ (2005) Response dynamics: Measurement of the force and rhythm of motor responses in laboratory animals. In: LeDoux M (ed) Animal models of movement disorders. San Diego, CA: Academic, pp 73–100

    Google Scholar 

  • Fowler SC, Birkestrand B, Chen R, Vorontsova E, Zarcone TJ (2003) Behavioral sensitization to amphetamine in rats: changes in the rhythm of head movements during focused stereotypies. Psychopharmacology 170:67–177

    Article  Google Scholar 

  • Fowler SC, Birkestrand BR, Chen R, Moss SJ, Vorontsova E, Wang G, Zarcone TJ (2001) A force-plate actometer for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies and tremor. J Neurosci Methods 197:107–124

    Article  Google Scholar 

  • Han DH, Kelly KP, Fellingham GW, Conlee RK (1996) Cocaine and exercise: temporal changes in plasma levels of catacholamines, lactate, glucose, and cocaine. Am J Physiolo 270:438–444

    Google Scholar 

  • Hutt C, Hutt SJ (1970) Stereotypies and their relation to arousal. A study of autistic children. In: Hut SJ, Hutt C (eds) Behavior studies in Psychiatry, chapter 10. Pergamon, Oxford, pp 175–200

    Google Scholar 

  • Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 29:565–598

    Article  PubMed  CAS  Google Scholar 

  • Koeltzow TE, Vezina P (2005) Locomotor activity and cocaine-seeking behavior during acquisition and reinstatement of operant self-administration behavior in rats. Behav Brain Res 160:250–259

    Article  PubMed  CAS  Google Scholar 

  • Lyon M, Randrup A (1972) The dose response effect of amphetamine upon avoidance behavior in the rat seen as a function of increasing stereotypy. Psychopharmacologia 23:334–347

    Article  PubMed  CAS  Google Scholar 

  • Lyon ML, Robbins TW (1975) The action of central nervous stimulant drugs: a general theory concerning amphetamine effects. In: Essman W, Valzelli L, (eds) Current developments in Psychopharmacology, vol. 2. New York: Spectrum, 79–163

    Google Scholar 

  • Mutschler NH, Covington HE, Miczek KA (2001) Repeated self-administered cocaine “binges” in rats: effects on cocaine intake and withdrawal. Psychopharmacology 154:292–300

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DC

  • Piazza PV, Deroche-Gamonet V, Rouge-Pont F, Le Moal M (2000) Vertical shifts in self-administration dose–response functions predict a drug-vulnerable phenotype predisposed to addiction. J Neurosci 20:4226–4232

    PubMed  CAS  Google Scholar 

  • Pickens R, Thompson T (1968) Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther 161:122–129

    PubMed  CAS  Google Scholar 

  • Post RM, Weiss SR, Fontana D, Pert A (1992) Conditioned sensitization to the psychomotor stimulant cocaine. Ann N Y Acad Sci 28:386–399

    Article  Google Scholar 

  • Randrup A, Munkvad I (1969) Pharmacological studies on the brain mechanisms underlying two forms of behavioral excitation: stereotyped hyperactivity and “rage”. Ann N Y Acad Sci 159:928–938

    Article  PubMed  CAS  Google Scholar 

  • Randrup A, Munkvad I (1970) Biochemical, anatomical and psychological investigations of stereotyped behavior induced by amphetamines. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven, New York, pp 695–713

    Google Scholar 

  • Remie R, van Dongen JJ, Rensema JW (1990) Permanent cannulation of the jugular vein. In: van Dongen JJ (ed) Manual of microsurgery on the laboratory rat. Elsevier, Amsterdam, pp 159–169

    Google Scholar 

  • Skinner BF (1981) Selection by consequences. Science 213:501–504

    Article  PubMed  CAS  Google Scholar 

  • Tornatzky W, Miczek KA (2000) Cocaine self-administration “binges”: transition from behavioral and autonomic regulation toward homeostatic dysregulation. Psychopharmacology 148:289–298

    Article  PubMed  CAS  Google Scholar 

  • Vanderschuren LJMJ, DiCiano P, Everitt, BJ (2005) Involvement of dorsal striatum in cue-controlled cocaine seeking. J Neurosci 25:8665–8670

    Article  PubMed  CAS  Google Scholar 

  • Weeks JR (1962) Experimental morphine addiction: method for automatic intravenous injections in unrestrained rats. Science 138:143–144

    Article  PubMed  CAS  Google Scholar 

  • Weiss SJ, Kearns DN, Cohn SI, Schindler CW, Panlilio LV (2003) Stimulus control of cocaine self-administration. J Exp Anal Behav 79:111–135

    Article  PubMed  Google Scholar 

  • Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA, Pickens R (1973) Self-administration of optical isomers of amphetamine and methylamphetamine by rats. J Pharmacol Exp Ther 187:27–33

    PubMed  CAS  Google Scholar 

  • Yokel RA, Wise RA (1978) Amphetamine-type reinforcement by dopamine agonists in the rat. Psychopharmacology 58:289–296

    Article  PubMed  CAS  Google Scholar 

Download references

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Correspondence to Stephen C. Fowler.

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Supported by DA002632 (KAM) and HD02528 (SCF)

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Fowler, S.C., Covington, H.E. & Miczek, K.A. Stereotyped and complex motor routines expressed during cocaine self-administration: results from a 24-h binge of unlimited cocaine access in rats. Psychopharmacology 192, 465–478 (2007). https://doi.org/10.1007/s00213-007-0739-6

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  • DOI: https://doi.org/10.1007/s00213-007-0739-6

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