benzoylecgonine and Body-Weight

Contradictory effects of ovarian hormone on cocaine-induced behaviors have been reported in ovariectomized Fischer rats. To determine if these discrepancies are based on where the rats were purchased, Charles River Laboratories and Taconic Fischer rats were randomly assigned to either cocaine (15 mg/kg, intraperitoneal) or saline treatment; and one of four hormone-pretreatment subgroups: vehicle, estrogen, progesterone or estrogen + progesterone. Vendor differences were observed in cocaine-induced locomotor activities; overall, Taconic rats demonstrated less locomotor activity than Charles River rats. Furthermore, vendor differences in ambulatory activity were also observed after steroid replacement treatment. In Charles River rats, estrogen + progesterone co-administration suppressed cocaine-induced increases in ambulatory activity when compared to other hormone-treated groups given cocaine. In contrast, Taconic rats showed an increase in ambulations after this drug/hormone treatment. Vendor differences were also observed in steroid effects on cocaine-induced rearing activity, where estrogen + progesterone and cocaine caused an increase in rearing in Charles River rats, but not in Taconic rats. No differences between the vendors were observed in saline- or cocaine-treated animals' stereotypic activity. Vendor differences in cocaine-induced locomotor activity were not due to differences in cocaine metabolism, as no differences in plasma levels of benzoylecgonine were observed. Interestingly, Taconic animals had overall higher plasma levels of corticosterone than Charles River rats. Thus, intrinsic differences between different lines of Fischer rats may affect the outcome of ovarian hormone interactions in cocaine-induced behavioral alterations.

Topics: Animals; Behavior, Animal; Body Weight; Cocaine; Corticosterone; Dopamine Uptake Inhibitors; Estrogens; Female; Locomotion; Ovariectomy; Progesterone; Rats; Rats, Inbred F344; Species Specificity

Previous investigations of metal/cocaine interactions have shown that chronic oral exposure to inorganic lead or cadmium attenuates the psychoactive effects of acute or repeated administration of cocaine. The purpose of this investigation was to assess the possibility that such interactive effects may derive from metal-induced disturbances in cocaine pharmacokinetics, i.e., delivery of cocaine to critical biologic sites may be disrupted by metal contamination. In this study, adult male rats were exposed to purified diets containing 250 ppm lead acetate (Group Lead), 100 ppm cadmium chloride (Group Cadmium), or unadulterated laboratory chow (Group Control); n = 48/exposure condition. Following ad libitum access to their respective diets in the home cage for 45 days, half the animals from each exposure regimen received single daily IP injections of 5, 10, or 20 mg/kg cocaine HCl for a period of 7 days (n = 8/group). The remaining half the animals received repeated daily injections of saline during this pretreatment phase. On the day following pretreatment, animals previously receiving cocaine injections were administered a single cocaine test challenge at a dose equal to that received in pretreatment. Similarly, saline pretreatment animals received either 5, 10, or 20 mg/kg cocaine. The results of this investigation did not reveal reliable evidence of metal-related differences in brain levels of cocaine. Plasma cocaine and benzoylecgonine (BE) levels also were essentially the same for control and metal-exposed animals. The failure to show that lead or cadmium alters the disposition of cocaine in brain or plasma underscores the need to pursue alternative accounts of metal/cocaine interactions.

Topics: Animals; Body Weight; Brain; Cadmium Chloride; Cocaine; Corpus Striatum; Dose-Response Relationship, Drug; Drug Interactions; Eating; Injections, Intraperitoneal; Male; Narcotics; Nucleus Accumbens; Organometallic Compounds; Rats; Rats, Sprague-Dawley

We determined the prevalence of cocaine and opiate exposure and the association of exposure with objective physical findings in children presenting to an urban pediatric emergency department. The study included 942 children between one and 60 months of age who required urinalysis for investigation of their chief complaint. Anonymously and without informed consent, urine was screened for benzoylecgonine (BE) and opiates, using an enzyme multiplied immunoassay technique (EMIT) with sensitivity of 50 ng/ml. EMIT-positive samples were rescreened using a fluorescence polarization immunoassay (FPIA). Specimens positive by both EMIT and FPIA were confirmed by gas chromatography/mass spectrometry (GC/MS) if sufficient quantity of urine was available. BE was identified in 41 (4.4%) and opiates in 46 (4.9%) patients by both EMIT and FPIA. The presence of BE or opiate was confirmed by GC/MS in all 34 cases where sufficient urine was available. The age- and sex-adjusted systolic and diastolic blood pressure percentiles were greater, and head circumference and weight percentiles were lower in BE-positive patients compared to those with negative drug screens. There were no associations between opiate exposure and any of these variables. We conclude that occult postnatal cocaine exposure is associated with measurable physical and physiologic differences.

Topics: Blood Pressure; Body Constitution; Body Weight; Child; Child, Preschool; Cocaine; Emergency Service, Hospital; Environmental Exposure; Female; Head; Humans; Infant; Infant, Newborn; Male; Michigan; Narcotics; Pediatrics; Prospective Studies; Urban Population

Adult rats that were gestationally exposed to cocaine and control offspring were examined for their sensitivity to challenge doses of cocaine. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg per 3 cc cocaine hydrochloride daily on gestational days 8-20, pair-fed dams that were injected with saline, and nontreated control dams. In order to investigate the sensitivity to challenge doses of cocaine, offspring were assessed in adulthood for locomotor activity, cocaine drug discrimination, and the time course of cocaine in brain tissue following acute cocaine challenge. Adult offspring prenatally exposed to cocaine were observed to exhibit a reduced sensitivity to the discriminative stimulus effects of cocaine as evidenced by a significant shift to the right in the dose-response curve of cocaine discrimination. No prenatal treatment effects were observed in terms of the temporal patterns of cocaine discrimination or with regard to brain levels of cocaine. In addition, baseline locomotor activity and locomotor responses to challenge doses of cocaine were comparable across the prenatal treatment groups. Thus, prenatal cocaine exposure reduced sensitivity of offspring to the discriminative stimulus properties of cocaine without altering either the distribution of cocaine to the brain or the sensitivity of the offspring to the locomotor stimulant effects of cocaine.

Topics: Animals; Behavior, Animal; Body Weight; Brain; Cocaine; Discrimination, Psychological; Dose-Response Relationship, Drug; Drinking; Eating; Female; Injections, Subcutaneous; Male; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sex Characteristics; Weight Gain

Although a common drug of abuse, cocaine's effects on cyclic reproductive functions and the neuroendocrine systems regulating these functions have not been studied. Here, we report the effects of cocaine on (1) estrous cyclicity and ovulation rates and (2) the stimulated in vitro release of hypothalamic GnRH and aminergic neurotransmitters directly involved in regulating or modulating GnRH release. Within 7 days of treatment with 10 mg kg-1 day-1 of cocaine HCl subcutaneously, rats demonstrated significant estrous cycle irregularity including repetitive days of estrus and prolonged periods of diestrus. After 6 weeks of treatment, cocaine-treated rats exhibited a 44.3% decrease in ovulation rates. For the in vitro studies, bilaterally ovariectomized rats were injected with cocaine (10 mg kg-1 day-1) or with saline for 2 weeks. Each rat received estradiol benzoate (50 mg kg-1 day-1 s.c.) for 2 days before sacrifice. Hypothalamic slices were prepared, placed in 0.1 ml microchambers and perfused with modified Krebs buffer (pH 7.4) using a programmable perfusion system. Basal release of norepinephrine (NE) and serotonin (5HT) was significantly increased in the cocaine-treated group versus controls. Ten-minute pulses of 10(-7)M progesterone (P4) increase NE and 5HT, but not dopamine (DA), release in the saline-treated group. In contrast, pulses of P4 increased NE, but not 5HT or DA, in the cocaine-treated rats. Ten-minute pulses of 0.1 microM NE increased GnRH release in both saline- and cocaine-treated rats. However, the response to pulsed NE was significantly attenuated in the cocaine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Behavior, Animal; Body Weight; Cocaine; Dopamine; Estrus; Female; Follicle Stimulating Hormone; Hypothalamus; Luteinizing Hormone; Neurosecretory Systems; Norepinephrine; Ovulation; Pituitary Hormone-Releasing Hormones; Prolactin; Rats; Serotonin

Cocaine hydrochloride (0 to 30 mg/kg, s.c.) was administered daily for a minimum of 72 days to Long Evans rats. Animals receiving the lower doses were pair fed to animals receiving the higher dose. Males were bred to untreated females. Paternal cocaine administration did not affect litter size, birth weight, or weight at weaning, but did result in offspring hyperactivity. A similar study was conducted for paternal alcohol consumption in Long Evans rats. Males consumed alcohol (35%, 17.5% or 0% ethanol derived calories) for 8 to 9 weeks and were then bred to untreated females. Males consuming the lower concentrations were pair fed to 35% EDC animals. Paternal alcohol consumption did not affect birth weight or weight at weaning but resulted in offspring hypoactivity. Mice sired by alcohol-consuming males were also hypoactive.

Topics: Animals; Birth Weight; Body Weight; Cocaine; Estradiol; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Fetal Resorption; Male; Mutagens; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Sex Factors; Testosterone