Cocaine self-administration in male and female rats perinatally exposed to PCBs: Evaluating drug use in an animal model of environmental contaminant exposure.

Abstract

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (i.v. SA) for the psychostimulant cocaine. Long Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared to non-exposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25 – 500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures.

Neurobehavioural and cognitive effects of prenatal exposure to organochlorine compounds in three year old children

“…Sex-linked differences as reported here, in other human studies [10,11,[56][57][58] and in animal studies [59][60][61][62] might result from oestrogenic and anti-oestrogenic actions [4,63,64] as oestrogens are essential in the neurogenesis and functionality of neurons which are important in learning processes and behaviour such as anxious and genderspecific behaviour [5,65]. In mammalians, the ontogenetic evolution towards the female phenotype appears in some way to be the default process and occurs to a large extent without sex hormone influence [12], while even small differences in levels and timing of exposure to hormones or endocrine disruptors may disrupt brain sexual differentiation [12].…”

Binge-like acquisition of α-pyrrolidinopentiophenone (α-PVP) self-administration in female rats

“…Female rats will self-administer more cocaine (Roth and Carroll 2004b; Smith et al 2011) and more methamphetamine (Reichel et al 2012; Roth and Carroll 2004a) than male rats (see (Anker and Carroll 2011; Lynch 2017) for reviews), however the IVSA of entactogen stimulants such as mephedrone, methylone and 3,4-methylenedioxymethamphetamine (MDMA) does not differ substantially between male and female rats (Creehan et al 2015; Vandewater et al 2015). Other studies have failed to find any sex-difference in IVSA of cocaine in rats (Miller et al 2017; Perry et al 2013) or the oral self-administration of cocaine in mice (DePoy et al 2016) and in some cases male rats may acquire cocaine IVSA more rapidly and in higher proportion compared with female rats (Swalve et al 2016a). These findings caution against simple assumptions about sex differences in drug IVSA and recommend investigation of the abuse liability of novel drugs in female as well as male rats to establish similarities and differences that might exist.…”

Binge-like Acquisition of α-pyrrolidinopentiophenone (α-PVP) Self-Administration in Female Rats

“…Female rats will self-administer more cocaine (Roth and Carroll 2004b;Smith et al 2011) and more methamphetamine (Reichel et al 2012; Carroll 2004a) than male rats (see (Anker and Carroll 2011;Lynch 2017) for reviews), however the IVSA of entactogen stimulants such as mephedrone, methylone and 3,4-methylenedioxymethamphetamine (MDMA) does not differ substantially between male and female rats . Other studies have failed to find any sex-difference in IVSA of cocaine in rats (Miller et al 2017;Perry et al 2013) or the oral self-administration of cocaine in mice (DePoy et al 2016) and in some cases male rats may acquire cocaine IVSA more rapidly and in higher proportion compared with female rats (Swalve et al 2016a). These findings caution against simple assumptions about sex differences in drug IVSA and recommend investigation of the abuse liability of novel drugs in female as well as male rats to establish similarities and differences that might exist.…”