Effects of perinatal oxycodone exposure on the cardiovascular response to acute stress in male rats at weaning and in young adulthood

Abstract

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress.Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood.Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males were fitted with BP telemetry units. Offspring were classically conditioned by following a pulsed tone (CS+) with tail shock. A steady tone (CS−) was not followed by shock. BP and HR were recorded during resting periods and conditioning. Changes in BP, HR from composite analysis were compared. The paradigm was repeated on PD 75.Results: At PD 40, OXY rats had a lower baseline mean BP (OXY: 114.8 ± 1.0 vs. CON: 118.3 ± 1.0 mm Hg; mean ± SEM) but larger amplitude of the conditional BP increase during the stress response (OXY: +3.9 ± 0.4 vs. CON: +1.7 ± 0.4 mm Hg). Both OXY and CON rats were able to discriminate between CS+ and CS−. At PD 75, the effects of OXY on the increased amplitude of the conditional BP had dissipated (CON: +3.4 ± 2.3 vs. OXY: +4.5 ± 1.4 mm Hg). BP responses to the stress and non-stress stimuli did not differ in the OXY group, suggesting that OXY may have decreased the ability of the offspring to discriminate (OXY: CS+: 147.1 ± 1.6, CS−: 145.9 ± 1.6 mm Hg vs. CON: CS+: 155.4 ± 2.7, CS−: 147.8 ± 2.7 mm Hg).Conclusion: POE is associated with subtle alterations in stress CV responses in weanling rats which dissipate when the conditioning is repeated at an early adult age. Although POE effect on the ability to discriminate at weanling age could not be detected, POE may impair retention of this ability in adulthood.

Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure

“…From our own literature search on MEDLINE, we identified radiotelemetric MAP measurements in 11 of the 47 species included in the 2 meta‐analyses . For the remaining 36 species, we were unable to find similar measures.…”

Enduring consequences of perinatal fentanyl exposure in mice

“…57 Children ages 6 to 13 that were exposed to prenatal opioids exhibit affective behavioral deficits. 44 Analogous outcomes are present in rodent models of early opioid exposure with offspring displaying hyperactivity, 58 cognitive deficits, 28 depressive-and anxiety-like behavior. 11,12 In our model, perinatal fentanyl exposure resulted in aberrant affective behaviors persisting into adolescence, evidenced by their performance on the splash test and the elevated plus maze.…”

Vascular flow reserve as a link between long-term blood pressure level and physical performance capacity in mammals

“…) data are included only from experiments where mean arterial pressure (MAP) has been measured telemetrically in chronically instrumented, conscious, and nonstressed animals. Species included are: dog (Haushalter et al 2008), rat (Sithisarn et al 2013), rabbit (Guild et al 2012), guinea pig (Hess et al 2007), mouse (Kim et al 2008), cynomolgus monkey (Haushalter et al 2008), sheep (King et al 2007), Yucatan miniature swine (Myrie et al 2012), G€ ottingen minipig (Stubhan et al 2008), Rhesus monkey (Regan et al 2009), marmoset (Wood et al 2005), horse (body mass estimated) (Hornicke et al 1977), three-toed sloth (Duarte et al 2003) and human (Damkjaer et al 2014). Human data are not telemetric.…”