title: Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning.
abstract: Individual differences in coping with novelty and in the response to psychoactive drugs have been related to early life events, such as the age of weaning. Outbred CD-1 mice underwent a precocious (postnatal day (pnd) 15, Wean-15 group), regular (pnd 21, Wean-21 group), or delayed (pnd 27, Wean-27 group) weaning, and were tested as adults (pnd > 60). In Experiment 1, animals underwent a treatment history with d-amphetamine (AMPH 0, 1, or 5 mg/kg once/day for three days) in a familiar environment. On testing day, mice were challenged with SAL or a standard 1 mg/kg AMPH dose (to evaluate acute drug effects and sensitization), and placed in the familiar environment. As expected, regular Wean-21 animals showed an AMPH-induced hyperactivity and a profile of conditioned locomotion, whereas the same dosage failed to induce any change in Wean-15 and Wean-27 groups. Levels of spontaneous novelty seeking were particularly elevated for Wean-27 mice, when compared with the other weaning groups. In Experiment 2, pairing of AMPH administration (0, 1, 2, 3.3, or 5 mg/kg once/day for three days) with a distinct environment produced a classical conditioned place preference. The magnitude of the preference profile was significantly more marked for Wean-15 mice, when compared with the other two weaning groups. Both experiments also provided evidence that the development of sensitization was particularly evident in Wean-27 mice. In summary, delayed weaning was associated in adult mice with both elevated levels of novelty seeking and increased sensitization to drug effects. Conversely, animals weaned precociously were much more responsive to AMPH-induced incentive conditioning. These results appear relevant to the issue of early experiences as possible risk factors for a number of psychiatric disorders in humans, including the abuse of drugs.
authors.affiliation: Section of Behavioural Pathophysiology, Lab. Fisiopatologia O.S., Istituto Superiore di Sanitá, viale Regina Elena 299, Roma, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000503:physiopathology / Q000523:psychology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D014886:Weaning
chemical_list: D000661:Amphetamine