The effect of exposure to drugs on the processing of natural rewards

in Neuroscience & Biobehavioral Reviews (2009), 33(3), 314-335

Why does moderate exposure to a drug reward make natural rewards increasingly attractive to organisms, whereas prolonged exposure to the same drug reward has the opposite effect? The paradox behind that ... [more ▼]

Why does moderate exposure to a drug reward make natural rewards increasingly attractive to organisms, whereas prolonged exposure to the same drug reward has the opposite effect? The paradox behind that question remains unsatisfactorily captured by current theories of addiction. The incentivesensitisation theory is viewed as a promising approach to this paradox, although it provides no mechanism to explain the decrease in interest of natural rewards as time exposure to a drug increases. To attempt to remedy this problem, I describe a model called the anticipatory dynamics model (ADM) that suggests a pivotal role of anticipation and attention inmotivational interactions. In addition to relying on strong neuropsychopharmacological data, the ADM provides an original conception of motivational specificity. The ADM is an extension of the incentive-sensitisation theory that hypothesizes how drugs interact with natural rewards. It has not been tested empirically, although a possible experiment to test two predictions in the field of addiction is presented. [less ▲]

Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents

in Neuroscience & Biobehavioral Reviews (2003), 27(1-2), 163-178

The present review deals mainly with the ontogenesis of two important phenomena involved in vulnerability to several neuropsychiatric disorders, namely with drug-induced sensitization (both contextual and ... [more ▼]

The present review deals mainly with the ontogenesis of two important phenomena involved in vulnerability to several neuropsychiatric disorders, namely with drug-induced sensitization (both contextual and non-contextual) and with conditioned place preference. The term 'infancy' covers the first three postnatal weeks during development in rats and mice. Conversely, the term 'adolescence' may cover the whole postnatal period ranging from weaning (PND 21) to adulthood (at least PND 60) or specifically the period around the onset of puberty (animals aged 33-44 days). Recent studies in rats demonstrated that the establishment of a context-dependent sensitization appears during the first (for repeated drug administration) or during the second (for a single drug administration) postnatal week. However, the memory of drug-context association is transient in developing pups (lasting one or two days following the drug pretreatment). The long-term retention of drug-context associations matures progressively, and is complete by the third week of postnatal life. Finally, those mechanisms responsible for an adult-like profile of context-independent pharmacological sensitization appear later during ontogenesis, being mature by the fourth week of postnatal life. Another set of experiments extended this ontogenetic characterization by comparing adolescent and adult mice. When compared to the latter, the former subjects exhibit a greater amphetamine-induced locomotor sensitization, almost no sensitization of aversive stereotyped behaviors, and a less marked place conditioning. The strength of the drug-induced place conditioning was also directly compared with the unconditioned novelty-seeking drive. In conclusion, neonatal rats are able to show a relatively short-lasting retention of sensitized drug effects (short-term sensitization), whereas the ability to exhibit relatively long-lasting sensitized effects matures progressively during infancy (long-term sensitization). On the other hand, adolescent mice show a reduced sensitization of drug-induced psychotic symptoms, together with a more marked sensitization of arousing and euphorigenic properties of the drug and a reduced incentive memory of its hedonic effects. These age-related changes do imply very different degrees of vulnerability to drug addiction and several other neuropsychiatric disorders. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲]

Antipsychotics and Neuropeptides: The Atypical Profile of Ci-943 and Its Relationship to Neurotensin

in Neuroscience & Biobehavioral Reviews (1995), 19(4, Winter), 519-31

CI-943 is a new drug candidate with antipsychotic-like activity in a variety of behavioural tests in rodents and primates, but without any affinity for brain dopamine receptors. CI-943 does not cause ... [more ▼]

CI-943 is a new drug candidate with antipsychotic-like activity in a variety of behavioural tests in rodents and primates, but without any affinity for brain dopamine receptors. CI-943 does not cause dystonia in monkeys, a predictive symptom of extrapyramidal side effects (EPS). Its mechanism of action remains unclear. Neurotensin (NT) concentration in nucleus accumbens and caudate is increased by CI-943; this may be associated with its antipsychotic effect. Indeed various observations suggest that the clinical action of antipsychotic drugs may at least be partially mediated by some neuropeptides. Various actions of neurotensin are reviewed. The hypothesis on the role of neurotensin represents a new strategy in the development of pharmacological tools for the treatment of schizophrenia. [less ▲]