Abstract
One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the auditory startle response (ASR), habituation, and prepulse inhibition (PPI) in the offspring. Nulliparous Long–Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC) from gestation day (GD) 8–20 (1×/day-GD8–14, 2×/day-GD15–20). COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18–20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg). When reassessed in adulthood (D90–100), a linear dose–response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval and induced significant sex-dependent changes in response latency. Idazoxan, an α2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.
Highlights
A variety of data sources suggest that the years of 1979– 1985 marked the height of the past epidemic of cocaine abuse in the U.S, the extraordinary levels of cocaine availability, increased purity, and the facility of smoking “crack” continue to captivate a significant segment of our population
Administration of cocaine to pregnant rats from the time of implantation until parturition produced significant alterations in auditory information processing in the Long–Evans rat within auditory startle, habituation, and reflex modification paradigms
Three prominent effects observed were: (1) the magnitude of the auditory startle response (ASR), as indexed by waveform amplitude, was significantly increased as a function of prenatal dose of cocaine; (2) decreased rates of within-session habituation were observed at even the lowest maternally administered dose; and (3) differential sensitivity to prepulse inhibition (PPI) was noted as a function of prenatal cocaine with manipulation of the interstimulus intervals (ISIs) function; this differential sensitivity of the preattentive process of sensorimotor gating was observed for both response amplitude and response latency measures
Summary
A variety of data sources suggest that the years of 1979– 1985 marked the height of the past epidemic of cocaine abuse in the U.S, the extraordinary levels of cocaine availability, increased purity, and the facility of smoking “crack” continue to captivate a significant segment of our population. In 2009, an estimated 21.8 million Americans aged 12 or older were current (past month) illicit drug users, meaning they had used an illicit drug during the month prior to the survey interview (Substance Abuse and Mental Health Services Administration, 2010). This estimate represents 8.7% of the population aged 12 years old or older. Illicit drug abuse, including cocaine/crack use, among young women of childbearing age remains a significant societal concern, placing future generations at risk. Comprehending the effects of prenatal drug exposure, such as cocaine/crack, on behavioral and neural development remains extremely important
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