Taking Rapid and Intermittent Cocaine Infusions Enhances Both Incentive Motivation for the Drug and Cocaine-induced Gene Regulation in Corticostriatal Regions.

A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours.

Role of the orbitofrontal cortex and the dorsal striatum in incentive motivation for cocaine.

Drug addiction involves increased incentive motivation for drug. Intermittent access to cocaine (IntA; 5-6 minutes ON, 25-26 minutes OFF, for 5-6 hours/session) enhances motivation to take the drug. The orbitofrontal cortex (OFC) and the dorsal striatum (DS) are part of a corticolimbic circuit that encodes incentive value and regulates reward-directed behaviour.

Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum.

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs.

Neurotensin in the nucleus accumbens reverses dopamine supersensitivity evoked by antipsychotic treatment.

Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors.

How fast and how often: The pharmacokinetics of drug use are decisive in addiction.

How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction.

The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake.

Rationale: Rapid drug delivery to the brain might increase the risk for developing addiction. In rats, increasing the speed of intravenous cocaine delivery (5 vs. 90 s) increases drug intake and the subsequent motivation to self-administer cocaine.

The speed of cocaine delivery determines the subsequent motivation to self-administer the drug.

The rapid delivery of drugs of abuse to the brain is associated with an increased likelihood and severity of addiction. Here we evaluated the hypothesis that rapidly delivered cocaine facilitates the addiction process by promoting the development of enhanced motivation for the drug. Rats lever-pressed for cocaine delivered intravenously over 5 or 90 s under fixed ratio (FR) during 6-h sessions.

Cues paired with either rapid or slower self-administered cocaine injections acquire similar conditioned rewarding properties.

The faster drugs of abuse reach the brain, the more addictive they can be. It is not known why this is. Environmental stimuli associated with drugs can promote the development and persistence of addiction by invigorating and precipitating drug-seeking behaviour.