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.

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

“…Specifically, changes in dopaminergic function in the medial frontal cortex have previously been shown to correlate with impaired forelimb movement and beam walking and with excessive grooming (Homberg et al, 2002;Urakawa et al, 2007). Increased dopaminergic function has been implicated in the pathophysiology of chorea (for review, see Gordon, 2009), and a decrease in plasma levels of catecholamine metabolites has been found in SC patients (Umene et al, 2007), which correlates with the present finding of a decrease in the level of one of the dopamine metabolites (HVA).…”

Animal models of drug addiction: Where do we go from here?

“…These may include changes in the likelihood that an individual will experiment with drugs, experience anxiolytic effects with early drug use, continue drug use despite adverse consequences, develop compulsive behaviours, exhibit disinhibited drug intake, self-medicate withdrawal symptoms, and so on. These processes may be dissociable in that high levels of depression, anxiety, and stress all predict drug self-administration (Homberg et al, 2002;Markou, 1998), but the three conditions are associated with distinct neurochemical profiles.…”

Higher locomotor response to cocaine in female (vs. male) rats selectively bred for high (HiS) and low (LoS) saccharin intake

“…Examples of drug-seeking-prone behaviors are voluntary or forced reactivity to a novel environment (Piazza et al, 1989(Piazza et al, , 1990(Piazza et al, , 2000Bardo et al, 1996;Klebaur and Bardo, 1999;Klebaur et al, 2001;Mantsch et al, 2001;Cain et al, 2004), novelty choice (Cain et al, 2005), wheel-running (Larson and Carroll 2005a), higher intake of saccharin-and sucrose-adulterated foods or liquids (Gahtan et al, 1996;Gosnell, 2000;Gosnell and Krahn, 1992;Gosnell et al, 1995) and dietary fat (Marks-Kaufman and Lipeles, 1982;Krahn and Gosnell, 1991), impulsiveness for food reward (Perry et al 2005(Perry et al , 2007c, and stress reactivity (Piazza and LeMoal, 1996;Homberg et al, 2002). This approach to identifying drug abuse vulnerability factors can also be accomplished by selective breeding for the phenotype of interest, and similar results have emerged in the case of saccharin intake and drug self-administration (Dess et al, 1998;Carroll et al, 2002Perry et al, 2007a,b).…”