Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Abstract

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.

Intramuscular Route of Administration Increases Potency in Eliciting Cocaine-Induced Behavioral Sensitization

“…Similar to rodent models, previous research in quail replicates the findings that IP administration of chronic cocaine dose-dependently enhances locomotor activity and induces cocaine sensitization [10, 11]. Specifically, cocaine sensitization is evident with IP administration of cocaine ranging from doses of 10 to 23 mg/kg in both rodents and quail using similar procedures [e.g., 13, 14, 15, 11]. However, some studies show that IP injections of substances might have an estimated 23% miss rate and instead enter the kidney, small bowel, and intravascular system [16, 17].…”

“…Typically, in both rodents and quail, cocaine sensitization is measured during 30 min locomotor activity sessions with IP injections of cocaine [e.g., 14, 15, 11). Pinkston & Branch [22] gave 150 min cocaine locomotor activity sessions.…”

Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice

“…an open field) where repeated drug administration had taken place, they show an increased locomotor activity compared with those animals that did not receive repeated drug administration. This phenomenon, known as conditioned locomotion (CL), indicates that animals have learned to associate the environment (conditioned stimulus) with the drug-induced motor response (unconditioned response) developing an implicit memory (Galeano et al, 2013). The CPP paradigm has been extensively used to study the conditioned rewarding effects of addictive drugs by repeated pairing drug effects with an initially neutral context, resulting in an explicit memory of the remembered place as preferred or favouritefavorite (Tzschentke, 2007).…”

Genetic and perinatal risk factors for movement disorders

“…In comparison to control vaginal delivery and C-section only pups, PA (for 15 min) increased the sensitization response to cocaine, whilst PA (for 20 min) decreased sensitization. These results show that the length of PA influenced dopaminergic-mediated response in mature rats (Galeano, Romero et al 2013). Severe PA (for 20 minutes) impaired motor coordination on the rotarod test at 3 months.…”

“…Moderate PA (for 15 min) rats had a greater reduction in TH than controls, whilst the cocaine-induced changes seen after severe PA (for 20 min) were smaller than in controls. Neither cocaine nor PA altered the expression of the dopamine active transporter (Galeano, Romero et al 2013). Moderate PA (for 15 min) increased dopamine and DOPAC in the prefrontal dopaminergic system and NAcc of male rats; decreased both products in female 5.…”