Behavioral effects of phencyclidine and some of its metabolites in developing cats.

Chronic treatment with low doses (1-2 mg/kg) of phencyclidine (PCP) produces marked behavioral effects in the developing kitten. These effects are age-dependent. Under 21 days the major response consists of rostrocaudal forelimb movements. After this age the major responses are ataxic locomotion and waxy rigidity. In the present experiment the behavioral effect of subcutaneous injections of higher doses of PCP, two of its metabolites, phencylclohexylamine (PCA) and an alcohol (N-(5-hydroxypentyl)-1-phenycyclohexylamine) (AL) and one PCP analog (N-N-diethylaminophenylhexylamine (NND] were tested in kittens between 30-50 days of age. The behavior of the kittens was assessed from 10-15 min pre-injection to up to 5 hr postinjection and at 24 hr postinjection. The most intense responses were produced by PCP and NND and consisted of waxy rigidity (limbs in abnormal postures for extended time periods) with the animal completely immobile. PCA was less effective, producing only tremor and staggering followed by loss of hindlimb support. AL was the least effective producing minimal behavioral responses. These results indicate that some of the metabolites of PCP, while active, are not as potent as PCP itself. Subsequent testing indicated that behavioral tolerance to the effects of PCP, NND and PCA occurred after a single administration of these compounds.

3H-xylamine binds to presynaptic rat striatal membranes.

3H-xylamine (3H-XYL), an irreversible catecholamine uptake inhibitor, was incubated with rat striatal synaptosomes, and the membrane fraction was examined by fluorography of a sodium dodecyl sulfate-polyacrylamide gel. A number of peptides were labeled. To determine their location, the striatal dopaminergic presynaptic nerve terminals were destroyed by unilateral electrolytic lesions through the nigrostriatal fibers prior to 3H-XYL exposure. The 3H-XYL bound to membranes from lesioned striata was about 29% of that bound to control membranes, which is consistent with the 83% reduction in dopamine (DA) uptake and the 68% reduction in DA content in the lesioned tissue. The decrease in peptide-bound 3H-XYL paralleled the decrease in DA content, with the exception of a 45% decrease in binding to a 45K peptide. These data show that 3H-XYL binding is predominantly localized in the dopaminergic presynaptic nerve terminals of the striatum.

A parametric study of the behavioral effects of phencyclidine in adult cats.

Five adult cats received four doses of phencyclidine to determine the behavioral effects of this compound. On alternate weeks the animals received control injections of saline vehicle. Dose-dependent behavioral changes occurred in three general categories (posture, locomotor activity and stereotyped head movements). In small doses (0.1 and 0.5 mg/kg), major postural effects consisted of head and body tremors and loss of hindlimb support. In larger doses (1.0 and 2.0 mg/kg), the postural effects occurred more rapidly and became more severe as animals lost both forelimb and hindlimb support and ultimately became immobile. Small doses of phencyclidine produced decreases in locomotor activity, followed by increases. Larger doses produced initial increases in activity. Increases in head movement stereotypies were produced by all doses of phencyclidine.

Behavioral effects of D-amphetamine in developing cats.

The development of the behavioral effects of amphetamine was assessed in kittens of 1-53 days of age. Amphetamine-induced increases in locomotion occurred when animals were beyond 35 days of age. Stereotypic behavior was induced at all ages tested but the predominant type of stereotypy was age-related. From 1 to 14 days amphetamine induced licking. Pendular head movements occurred when animals were under 35 days. At 14 days of age darting, a response consisting of rapid pacing and turning began to occur. Tracking, a series of horizontal and vertical head movements also began to occur after 14 days. The adult response of vertical and horizontal head movements became most prominent after 35 days.

Differential effects of xylamine on extracellular concentrations of norepinephrine and dopamine in rat central nervous system: an in vivo electrochemical study.

The effects of xylamine (N-2-chloroethyl-N-ethyl-2-methylbenzylamine) on tissue content and extracellular concentration of catecholamines in the rat brain were examined after systemic administration using in vivo voltammetry and high-performance liquid chromatography-electrochemical detection. Xylamine at a dose of 12.5 mg/kg i.p. reduced the extracellular concentration of norepinephrine (NE) in the cortex, while having no effect on the extracellular concentration of dopamine in the striatum. The content of NE in the cortex was reduced by approximately 41% at a dose of 12.5 mg/kg and 62% at 25 mg/kg within a 4-hr period, whereas dopamine contents remained unaltered. Both the reduction in extracellular concentration and the depleting action of xylamine on NE content were blocked by pretreatment with desmethylimipramine. The data suggest that xylamine has a selective action on the NE system that is mediated through the neuronal uptake carrier; however, the depleting action of xylamine and its effect on extracellular NE concentration may be unrelated actions.

A comparison of CNS stimulants with phencyclidine on dopamine release using in vivo voltammetry.

Phencyclidine (PCP) produces some neurochemical and behavioral effects in rats similar to those produced by the indirectly acting dopamine (DA) agonists amphetamine and amfonelic acid. In view of these findings, the effects of PCP, d-amphetamine and amfonelic acid on the release of DA in the rat striatum were examined by in vivo voltammetry. Drug effects on DA release were determined using newly developed electrodes selective for catecholamines. PCP (5 and 10 mg/kg IP) produced a dose-dependent decrease in the electrochemical signal that lasted for approximately 4 hr. In contrast, d-amphetamine (2.5 mg/kg, IP) and amfonelic acid (5.0 mg/kg, IP) both caused marked increases in electrochemical signals. The data provide evidence that PCP at the doses tested alters dopaminergic neurotransmission in a manner different from that of amphetamine and the non-amphetamine central nervous system stimulants by decreasing DA release from dopaminergic nerve terminals.