Neonatal immune system activation with lipopolysaccharide enhances behavioural sensitization to the dopamine agonist, quinpirole, in adult female but not male rats

作者：Tenk Christine M^*; Foley Kelly A; Kavaliers Martin; Ossenkopp Klaus Peter

来源：Brain, Behavior, and Immunity, 2007, 21(7): 935-945.

DOI：10.1016/j.bbi.2007.03.001

• immune activation
• endotoxin
• lipopolysaccharide
• neonatal
• sex differences
• Sensitization
• dopamine agonist
• quinpirole
• drug addiction
• locomotor activity

Administration of the bacterial cell wall component, lipopolysaccharide (LPS), stimulates the immune and endocrine systems inducing an acute phase of sickness and stress responses in adult and neonatal rats. Neonatal LPS exposure has been shown to alter a variety of behavioural and physiological processes in the adult animal. Early developmental stress, such as maternal separation, causes similar acute as well as long-term behavioural changes in adults, including altered sensitivity to drugs of abuse. Moreover, results of studies have shown evidence of a direct link between immune activation and sensitivity to dopamine-based drugs of abuse. The current study examined the effects of neonatal LPS treatment on subsequent locomotor sensitization to the dopamine (D-2/D-3) agonist, quinpirole, in adult rats as an index of drug sensitivity. Male and female Long-Evans rats were treated systemically with either LPS (50 mu g/kg) or saline (0.9%) on postnatal days 3 and 5. Locomotor sensitization was then examined in the adult rats (postnatal day 70). Animals were injected with quinpirole (0.5 mg/kg, s.c.) or saline every other day for a total of 10 injections and locomotor activity was assessed for 60 min immediately following injections 1, 2, 4, 6, and 10. Animals also received a 'challenge' injection of 0.5 mg/kg quinpirole 28 days after injection 10, to assess persistence of behavioural sensitization. Locomotor activity progressively increased with repeated administration of quinpirole, indicating locomotor sensitization in all of the drug-treated groups. There was an overall sex difference, with females showing significantly greater sensitization than males. Moreover, neonatal LPS treatment potentiated both the level and the rate of development of locomotor sensitization to quinpirole administration in females, but not in males. Thus, the current study revealed that neonatal exposure to bacterial infection increases dopamine (D-2/D-3) agonist sensitivity in a sex-specific manner. These findings have important implications for the sexually dimorphic development of addictions to both natural and artificial rewards.

• 出版日期2007-10