title: Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.
abstract: Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.
authors.affiliation: * Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Camilla
authors.initials: C
authors.lastname: Lazzaretti
authors.affiliation: † Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Grasielle Clotildes
authors.initials: GC
authors.lastname: Kincheski
authors.affiliation: ‡ Universidade Federal Fluminense (UFF), Rio de Janeiro, RJ, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.affiliation: § Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.|¶ Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas (UCPel), Pelotas, RS, Brazil.
authors.forename: Rachel
authors.initials: R
authors.lastname: Krolow
authors.affiliation: § Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Toniazzo
authors.affiliation: § Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Danusa Mar
authors.initials: DM
authors.lastname: Arcego
authors.affiliation: § Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Natividade de Sá
authors.initials: Nde S
authors.lastname: Couto-Pereira
authors.affiliation: § Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Fares
authors.initials: F
authors.lastname: Zeidán-Chuliá
authors.affiliation: ∥ Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Martin
authors.initials: M
authors.lastname: Galvalisi
authors.affiliation: ** Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Costa
authors.affiliation: ∥ Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
authors.affiliation: * Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.|§ Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Tadeu Mello E
authors.initials: TM
authors.lastname: Souza
authors.affiliation: * Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.|§ Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Dalmaz
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D005260:Female; D006234:Handling, Psychological; D007175:Impulsive Behavior / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012737:Sex Factors; D013997:Time Factors
chemical_list: D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: ADHD; Neonatal handling; attention deficit hyperactivity disorder; impulsivity; manic behavior; monoamines; prefrontal cortex; psychiatric disorder