Ethanol, Morphine and Barbiturate Alter the Hemodynamic and Cerebral Response to Cocaine in Newborn Pigs

Abstract

Newborns delivered to cocaine-abusing mothers are often exposed to other concurrently consumed illicit drugs, which may alter the hemodynamic and cerebral response to cocaine. This study examined the interaction of ethanol, morphine or barbiturate with cocaine on mean arterial pressure (MAP), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) in newborn pigs. CBF, CMRO₂ and cerebral O₂ extraction (CECO₂) were measured before and 4 and 10 min after cocaine (1.5 mg/kg i.v.) was administered in piglets that were awake, or pretreated with morphine, ethanol or pentobarbital. In awake piglets, cocaine increased CMRO₂ and CEO₂ while it had no significant effect on CBF. Conversely, in morphine- and ethanol-pretreated piglets, cocaine decreased CMRO₂, decreased CBF and had not effect on CEO₂. In awake piglets, cocaine increased MAP, whereas in morphine- or ethanol-pretreated piglets, cocaine decreased MAP. In the pentobarbital group, cocaine had no effect. These data demonstrate that other drugs of abuse alter the hemodynamic and cerebral effects of cocaine in the immature animal and may contribute to the central nervous system abnormalities in ‘crack babies’.

Effect of Dopamine Antagonism on the Behavioral and Hemodynamic Responses to Cocaine in Piglets

“…In studies of conscious ani mals, hypertension is frequently observed within 2 min of cocaine administration [11,21,23]. The 10% increase in mean arterial blood pressure that we observed is compara ble to our prior results [14], but it is less than the 50% increase reported in adult rats and dogs following cocaine administration [21,23], The inability of SCH23390 to block the pressor response to cocaine suggests that D| receptor activation does not play an impor tant role in the pressor response to cocaine in newborn piglets. This conclusion is consistent with studies in adult rats and dogs in which adrenergic stimulation has been shown to me diate the hypertensive response to cocaine [20,21], blood flow have shown cocaine to increase, decrease, or not change the cerebral blood flow [9][10][11]14].…”

“…Some of this variability in results may be due to differences in experi mental methodology and species studied. We have previously shown cocaine to not change global or regional cerebral blood (low in awake, acutely instrumented piglets [14]. In terestingly, unlike that earlier study, we ob served an increase in blood flow in the cere bellum with cocaine in our awake, chronically instrumented piglets.…”

“…Subsequently, cocaine hydrochloride (1.5 mg/kg dissolved in 3 cm3 of lactated Ringer solution) was injected over 15 s into the jugular vein, and 4 min later behavior, mean arterial pressure, and blood flow were remeasured. Previous work in our laboratory [ 14] has shown that in piglets the maximal blood flow response to cocaine occurs by 4 min after cocaine administration.…”

“…Prior studies have demonstrated that the cardiovascular response to cocaine is fully ex pressed only when the central and peripheral nervous systems have not been altered by sed ative, analgesic, or autonomic antagonist drugs [14,23]. In studies of conscious ani mals, hypertension is frequently observed within 2 min of cocaine administration [11,21,23].…”

“…[10] demon strated that cocaine can act as either a cere bral vasoconstrictor or a vasodilator. Finally, cocaine can alter the cerebral metabolism [ 14] which may also play a role in its cerebrovascu lar effects.…”