Article Figures & Data
Figures
- Figure 1.
Gestational opioid exposure results in physiological alterations that persist throughout adulthood. A, Schematic representation of gestational opioid exposure. Pregnant rats received intraperitoneal injections of either buprenorphine (1 mg/kg), oxycodone (10 mg/kg), or saline from gestational day (GD) 11 through 21. Withdrawal symptoms were assessed on postnatal day (PD) 1. Rats were weaned on PD 21 then PPI and VTA dopamine neuron activity were assessed in adulthood (>12 weeks of age). B, Pups exposed to oxycodone and buprenorphine in utero displayed more withdrawal behavior than saline-treated pups; *p < 0.05 compared with saline. n = 7 rats per group. Additionally, gestational buprenorphine exposure resulted in more withdrawal behavior than gestational oxycodone exposure; #p < 0.05 compared with oxycodone. n = 7 rats per group. C, Body weight from weaning until adulthood was significantly reduced in oxycodone-treated and buprenorphine-treated animals; *p < 0.05 compared with saline, n = 13–16 rats per group. Further, buprenorphine rats displayed lower body weight than oxycodone rats; #p < 0.05 compared with oxycodone, n = 16 rats per group. This trend was the same in males (D) and females (E). F, Brain weight was measured in adulthood. Adult rats exposed to gestational oxycodone or buprenorphine exhibited lower brain weight compared with saline controls; *p < 0.05 compared with saline, n = 13–15 rats per group. The same trend was observed in adult males (G) but not adult females (H). Females exposed to oxycodone but not buprenorphine had lower brain weight in adulthood; *p < 0.05 compared with saline, n = 6–7 rats per group.
- Figure 2.
Prenatal opioid exposure results in PPI deficits in adulthood. Gestational exposure to oxycodone or buprenorphine produces adulthood deficits in PPI in male and female rats combined; *p < 0.05 compared with saline, n = 15–17 rats per group (A). When disaggregated by sex, there were no significant differences between the males (B). However, oxycodone-treated and buprenorphine-treated females (C) had significant deficits in PPI compared with saline; *p < 0.05 compared with saline, n = 7–9 rats per group.
- Figure 3.
Prenatal opioid exposure significantly increases dopamine neuron population activity in adulthood. Three parameters of dopamine neuron activity were measured in male and female rats combined: (A) population activity (average number of spontaneously active dopamine neurons per electrode track), (B) average firing rate, and (C) average percentage of spikes firing in a burst. Gestational oxycodone or buprenorphine exposure increases dopamine population activity in adulthood (A): *p < 0.05 compared with saline. There were no significant changes in firing rate (B) or bursting pattern (C). Representative traces from saline animals (D) oxycodone animals (E) and buprenorphine animals (F) n = 14–16 rats per group. Increased population activity was observed in males (G) and females (H) exposed to oxycodone or buprenorphine in utero; *p < 0.05 compared with saline.
- Figure 4.
Inhibition of afferent regulation of dopamine neuron activity does not reverse population activity in buprenorphine-treated adults. A, Schematic representation of the multisynaptic circuit by which the vHipp and PVT regulate dopamine activity in the VTA. In healthy animals, GABAergic projections from the ventral pallidum (VP) provide tonic inhibition of VTA dopamine neuron activity. In animal models used to study psychosis, increased activity of glutamatergic inputs from the vHipp or PVT to the NAc result in downstream hyperfunction of the dopamine system which can be reversed by selective injection of TTX. Representative cannula tracks, indicated by an arrow, in the vHipp (B) and PVT (C) and corresponding schematics of the brain section. D, Dopamine system function was restored following TTX inactivation of either the vHipp or PVT in oxycodone-treated animals but not buprenorphine-treated animals; *p < 0.05 denotes significant difference from control oxycodone animals. There were no changes in the firing rate (E) or percentage of cells bursting (F) in any treatment.
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