title: Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala.
abstract: Rats, like humans, show strong individual differences in their response to anxiogenic and stressful stimuli. In the present study we evaluated whether differences in stress-induced self-grooming behaviour may predict an individual's vulnerability to engage in drug self-administration behaviour. From a population of Wistar rats, the lower and upper quartile with respect to time spent self-grooming on an elevated plus maze (EPM) were selected and trained to intravenously self-administer cocaine under fixed and progressive ratio schedules of reinforcement. High grooming (HG) rats reached considerably higher breakpoints than low grooming (LG) rats but showed no differences in acquisition rate and dose-response relationships. Further, EPM exposure elicited higher anxiety levels and enhanced plasma corticosterone secretion in HG rats. In addition, HG rats did not display enhanced novelty-seeking and still spent more time self-grooming during an EPM re-test following the cocaine self-administration procedure, indicating that stress-induced self-grooming is a stable behavioural trait marker. Neurochemically, electrically evoked [(3)H]dopamine release in vitro was profoundly lower in brain slices from the substantia nigra, medial prefrontal cortex and amygdala of naive HG rats as compared to LG rats, whereas no differences were found in the nucleus accumbens shell and core, the ventral tegmental area and caudate putamen. In conclusion, stress-induced self-grooming specifically predicts enhanced motivation to self-administer cocaine rather than sensitivity to its reinforcing effects. Responsiveness of dopaminergic nerve terminals in the medial prefrontal cortex and amygdala may represent pre-existing underlying factors.
authors.affiliation: Graduate School Neuroscience Amsterdam, Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, VU Medical Center, Van Der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.forename: Margot
authors.initials: M
authors.lastname: van den Akker
authors.forename: Halfdan S
authors.initials: HS
authors.lastname: Raasø
authors.forename: George
authors.initials: G
authors.lastname: Wardeh
authors.forename: Rob
authors.initials: R
authors.lastname: Binnekade
authors.forename: Anton N M
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: Taco J
authors.initials: TJ
authors.lastname: de Vries
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D009042:Motivation; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D003042:Cocaine; D004298:Dopamine; D003345:Corticosterone