Effect of prenatal maternal administration of d-amphetamine on rat offspring activity and passive avoidance learning

Abstract

Gravid albino rats were injected subcutaneously with 0, 5, or 10 mg/kg body weight of d-amphetamine during Days 5-9 or Days 12-16 of gestation. Offspring were assessed for activity level and passive avoidance learning. Almost all of the drug groups, especially those whose mothers received 5 mg of d'amphetamine early in pregnancy, displayed significantly higher activity than did the controls. Administration of 5 mg of d'amphetamine to mothers early in pregnancy was also detrimental to the learning of a passive avoidance response in their offspring, but large doses, whether given early or late in pregnancy, did not affect this behavior.The effect of early experience upon later behaviors of an organism is a currently highly researched area in the field of psychology; numbers of investigators have published results involving various stressor agents applied to the neonate, infant, and adolescent. It is apparent that a great deal of emphasis has been placed on the importance of events occurring early in life in determining later behavior. However, compared with the extensive literature concerning effects of stressors applied postnatally, there appear to be relatively few studies dealing with the effects on offspring behavior of agents administered prenatally, an area which Thompson, Watson, and Charlesworth (1962) have declared a logical extension of the early environment problem.Of the wealth of medical articles dealing with the teratogenic effects of various agents, the majority restricts their reports to anatomical and physiological defects of offspring. If there are no obvious malformations, the compound is considered to be safe. As Werboff and Gottlieb (1963) have stated, another system is susceptible to teratogenic effects of drugs-the behavior, or functional adaptation, of the offspring to its environment. If the developing fetus can be affected by stressor agents, it is not unreasonable to suppose that these agents might influence the behavioral development and subsequent adjustment of the organism.Research has established that several treatments, when administered prenatally, can produce many behavioral changes in the offspring. Investigators have demonstrated the effects of drugs (Armitage, 1952;Hamilton, 1945 ;Hamilton & Hamed, 1944; Thompson, *This report is based on a dissertation submitted to Temple University in partial fulfillment of the requirements for the PhD degree. The author wishes to express gratitude to Hughbert C.Hamilton for his guidance and support throughQut this work. The author also thanks the Philadelphia College of Pharmacy and Science, and particularly Elias W. Packman, for making laboratory facilities so freely available for the conduct of this research. The experimental compound was generously supplied by Smith, Kline, and French Laboratories.t Requests for reprints should be sent to Deborah L. Seliger, who is now at Rutgers University, Camden, New Jersey 08102 . Goldenberg, Watson, & Watson, 1963; Werboff, Gottlieb, Dembicki, & Havlena, 1961; Werboff & Kesner, 1963), radiation (...

In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring

“…The number of male and female rats in each group are as follows: controls, males = 19, females = 10; high-dose methamphetamine, males = 6, females = 3; low-dose methamphetamine, males = 10. females = 7. contrast, other studies reported increased open field activity in rat offspring who, similar to the present study, received in utero amphetamine or methamphetamine throughout gestation and were tested following weaning. A major difference in our study was the use of a substantially higher dose of methamphetamine than in other studies (Martin and Martin, 1981;Nasello and Ramirez, 1978;Seliger, 1973). Our high-dose drug effects may resemble the long-term apathy and loss of initiative reported in some drug-free humans who had been chronic users of high doses of methamphetamine (Utena, 1966).…”

“…Because of continuous anatomical and biochemical changes during brain development, the use of different drug doses by various studies, different drug administration times, and different postnatal ages of testing, there is greater variability for in utero studies than for those using mature animals. For example, several studies reported increased open field behavior, increased active avoidance, and decreased Lashley I11 maze performance (Martin and Martin, 1981;Nasello and Ramirez, 1978;Seliger, 1973) when amphetamine was administered throughout the entire gestation period, drug doses were in a moderate range (0.5-5 mgl kg), and rats were tested after weaning. However, when amphetamine was administered for a restricted period during gestation or when preweanlings were tested, motor activity was either elevated (Hitzemann et al, 1976), not different (Adams et al, 1982;Middaugh et al, 1974;Monder, 1981), or reduced (Bell et al, 1965;Clark et al, 1970) as compared to controls.…”

Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits

“…1965;Clark etal. 1970;Seliger 1973;Middaugh et al 1974;Nasello et al 1974;Hitzemann et al 1976;Nasello and Ramirez 1978;Satinder and Sterling 1983;Holson et al 1985;Middaugh 1989) although some studies have shown no long-term effects on activity (Monder 1981;Adams et al 1982;BuelkeSam et al 1982;Vorhees 1985). Neurochemically, early postnatal exposure to MA or AMPH has been shown to induce smaller DA and 5-HT reductions than exposure in adults (Wagner et al 1981;Lucot et al 1982).…”

Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge

“…In rats, MA or amphetamine (AMPH) exposure during development is associated with long-term changes in locomotor activity and shock avoidance performance (for MA : Martin 1975;Martin et al 1976;Martin and Martin 1981;Sato and Fujiwara 1986; and for AMPH: Bell et al 1965;Clark et al 1970;Seliger 1973;Middaugh et al 1974;Nasello et al 1974;Hitzemann et al 1976; Nasello and Ramirez 1978;Monder 1981; Correspondence to: C.V. Vorhees et al 1982;Buelke-Sam et al 1982;Satinder and Sterling 1983;Holson et al 1985;Vorhees 1985;Middaugh 1989). Neurochemically, early postnatal exposure to MA or AMPH has been shown to induce smaller dopamine (DA) and serotonin (5-HT) reductions than exposure in adults (Wagner et al 1981 ;Lucot et al 1982).…”