The ontogeny of the classical conditioned leg flexion response in normal, dl para-chlorophenylalanine treated and radiothyroidectomized albino rats



Journal Title

Journal ISSN

Volume Title



Habituation and classical conditioning were investigated during the cortical developmental period in normal and experimentally analogous phenylketonuric and cretin rats. Three hundred and twenty Sis comprised 32 equal groups. These formed conditioning (Tl, T2, T3, and T4), pseudoconditioning (T5), drug control (T6 and T7), and normal control (T8) groups at four age levels designated Al, A2, A3, and A4. The Al Ss were tested at an average age of seven days, A2 at 14, A3 at 21, A4 at 28. The range of ages for each group was three days. Daily intubations of dl para chlorophenylalanine (dl PCL) suspended in a .20 per cent agar solution (Tl, T2, T6 and T7 groups), or of the vehicle (T3, 14, T5 and T8 groups), were initiated within eight hours after birth and discontinued 72 hours prior to conditioning (Tl to T5 groups) or 24 hours prior to sacrifice (T6 to T8 groups). Intubated volume was 10 ml/kg. Groups Tl and T6 received 150 mg/kg dl PCL with A3 and A4 levels being switched to 100 mg/kg on day 13. Groups T2 received 100 mg/kg dl PCL. At birth T3 groups were injected with 150 microcuries of radioactive iodine. Eight blocks of ten trials pairing a vibro-tactile conditioned stimulus (CS) and a shock unconditioned stimulus (UCS) and one block of only CS presentations were completed. Nonsystematic presentations of CS and UCS constituted a pseudoconditioning control. Anticipatory conditioned responses (ACR) and test conditioned responses (TCR) were recorded. Two periods of spontaneous leg flexion (SLF) were recorded to measure general activity. Five measures were recorded which were used to equate CS and UCS intensity levels for the individual SSs. The number of trials necessary to reach an habituation criterion for CS presentation was determined. Whole brain serotonin (5-HT) and norepinephrine (NE) and plasma phenylalanine were assayed for all Ss. Thyroid gland tissue for 14 T3 and 14 T4 Ss was histologically examined. Unless otherwise noted, the results designated as significant refer to p less than .01. The TCRs yielded significant treatment and age effects. Normal groups (T4) evidenced significantly superior conditioning. Conditioning level was significantly higher (p less than .05) for T4 Ss at A3 (21 days) than at Al or A2, while it did not differ from that at A4. The ACR data showed all factors, except treatment by age by block, to be significant. Age and treatment by age effects were significant in analysis of SLFs preceding conditioning. The SLF measures during conditioning yielded significant treatment and age effects. The five measures taken to establish CS and UCS levels yielded significant main and interaction effects. Analysis of the number of trials to reach an habituation criterion for CS presentation did not show significance. Brain NE and 5-HT data were significant for all factors. Brain 5-HT levels were significantly decreased for groups Tl, T2, T6, and T7 (dl PCL treated groups). Plasma phenylalanine data were significant for all factors. The levels were significantly higher in T6 and T7 (drug control) groups than in Tl and T2 (drug conditioning) groups which, in turn, had levels siginificantly higher than the other groups. Plasma phenylalanine and brain 5-HT levels demonstrated normal developmental patterns for T8 groups, while NE levels did not. Histological examination of thyroid tissue showed T3 Sis to be athyrotic. Comparison on all factors were significant for weight data. Groups Tl, T2, and T3 weighed significantly less than T4 and T5 with the differences increasing with age. The superior performance of 14 over T5 groups was interpreted as indicating that learning was measured by the experimental paradigm. The significant increase in TCRs obtained at 21 and 28 days indicated that conditionability increased with age during the cortical developmental period. The other data were interpreted as evidence that experimental analogs of phenylketonuria and cretinism were established and that these conditions were incompatible with the acquisition of conditioned responses. Biochemical data which support this interpretation showed 5-HT levels of the dl PCL treated groups to be significantly lower than those of the other groups and plasma phenylalanine levels to be significantly higher. Supporting anthropometric data showed Tl, T2, and T3 groups to weigh less than other groups. Supporting behavioral data showed Tl, T2, and T3 groups, at all ages, to manifest lower conditioning levels than normal Ss. Supporting histological evidence showed an absence of viable thyroid tissue in T3 Ss.



Phenylketonurias, Congenial hypothyrodism, Rats