Doses Of Phencyclidine Research Articles

Phencyclidine produces aggressive behavior in rapid eye movement sleep-deprived rats

This study examined effects of acute doses of phencyclidine (PCP; 0.025, 0.05, 0.10, and 0.20 mg/kg intraperitoneally) on intra-specific aggressive behavior and muricide in normal rats and rats deprived of rapid eye movement (REM) sleep. Dose-related changes in intra-specific aggression and muricide occurred in REM sleep-deprived rats only. Dose-response curves are inverted-U shaped with the .05 mg/kg dose producing increases in aggression. Intra-specific and muricide may serve as models of PCP-induced aggression in humans.

D-Amphetamine and phencyclidine alone and in combination: Effects on fixed-ratio and interresponse-time-greater-than-t responding of rats

The effects of three doses of d-amphetamine (0.5, 1.0, and 2.0 mg/kg) and phencylidine (0.5, 1.0, and 2.0 mg/kg), alone and in combination, were assessed in rats performing under fixed-ratio 30 and interresponse-time-greater-than-15-sec food reinforcement schedules. When given alone, phencyclidine and d-amphetamine produced similar increases in responding under the interresponse-time-greater-than-t schedule, and decreases in responding under the fixed-ration 30 schedule. Each drug decreased the number of reinforcers (food pellets) earned relative to control values under both schedules. The effects of the two drugs in combination were nearly always less than additive. That is, the effects of a given dose of phencyclidine and d-amphetamine together were less than an arithmetic summation of the effects of the drugs given alone.

Electrophysiological effects of phencyclidine on rat hippocampal pyramidal neurons

The effects of local application of phencyclidine to hippocampal CAl pyramidal neurons was investigated using electrophysiological techniques. The predominant response was a decrease in firing rate, although excitation and biphasic responses were also seen. The stereospecificity of these responses was demonstrated using the (+) and (−) isomers of 1-[1-phenylcyclohexy]-3-methylpiperidine (PCMP). The (+) enantiomer was 4–15 times more potent than the (−) enantiomer. Interactions between PCP and catecholaminergic synapses were also investigated. Catecholamine depletion by reserpine markedly increased the amount of phencyclidine needed to elicit effects on cell discharge; in many cases, no response was seen with the largest dose of phencyclidine tested. The α-adrenergic antagonist, phentolamine, reversibly antagonized phencyclidine-induced inhibition in the firing rate of CAl cells but did not seem to affect excitation; in contrast, timolol, a β-adrenergic antagonist, did not affect the depression but seemed to antagonize reversibly the phencyclidine-induced excitations. It is concluded that the mechanism of phencyclidine-induced changes in pyramidal neuron discharge involves adrenergic input to these cells.

Effects of acute and chronic administration of phencyclidine on tyrosine hydroxylase activity in rat striatum.

Following a single dose of phencyclidine (PCP) striatal tyrosine hydroxylase (TH) activity was decreased 42% 15 min after PCP administration, but returned toward baseline levels by 45 min post-drug. Twenty-four hours after the 30th dose of PCP, TH activity remained depressed when compared to the chronic slaine controls. TH activity was not further depressed 15 or 45 min after the 31st dose of PCP.

First dose behavioral tolerance to phencyclidine on food-rewarded bar pressing behavior in the rat.

The behavioral effects of single doses of phencyclidine (PCP) were examined in drug-naive adult male Holtzman rats trained to press a bar on a fixed ratio (4) schedule (FR4), i.e., a reward of sugarsweetened milk was earned on every fourth bar press. Groups of rats (four to eight rats per group) received specific doses of PCP which were held constant for each group throughout the study. Dose-response curves for PCP given in doses of 1.0, 1.8, 2.4, and 3.2 mg/kg IP were first determined and then redetermined at weekly intervals. A drug-free interval of 7–8 days was maintained between injections given weekly over a period of 4 weeks. The final dose of PCP was administered after a 4-week drug-free period. Evidence was obtained for first dose behavioral tolerance as shown by the significantly shortened duration of suppression of bar pressing on subsequent injections. Although subsequent weekly effects of equal doses of PCP showed no significant differences, they all differed significantly from the first injection. The reduced response to PCP was shown to be due to learned behavioral tolerance as demonstrated when PCP (3.2 mg/kg IP) was given to drug-naive animals in their home cages and 1 week later given the second dose in the operant behavioral situation. Under these circumstances, the second dose of PCP showed a similarly protracted depression of FR4 responding as other animals given the drug for the first time in the operant situation. Subsequent weekly injections in the operant situation produced similar behavioral tolerance.

Discriminative stimulus properties of phencyclidine

Rats were trained to discriminate intraperitoneal injections of phencyclidine (4.0 mg/kg) from saline in a two-lever drug discrimination task. After reliable discrimination was established and a dose-response curve was obtained, two doses of each of a variety of agents were tested to determine whether they evoked responding on the phencyclidine-appropriate lever. All doses of the indirect dopamine agonist d-amphetamine (0.5 and 1.0 mg/kg) and the direct dopamine agonist apomorphine (0.5 and 1.0 mg/kg), the direct serotonin agonists LSD (0.08 and 0.16 mg/kg) and quipazine (1.0 and 2.0 mg/kg), and the anticholinergic drugs atropine (0.5 and 1.0 mg/kg) and ditran (3.0 and 6.0 mg/kg) failed to produce phencyclidine-like discriminative effects, as did diazepam (8.0 and 16.0 mg/kg) and a 7.5 mg/kg dose of ketamine. A 15.0 mg/kg dose of ketamine, a compound structurally and pharmacologically similar to phencyclidine, did produce phencyclidine-like discriminative effects. The dopamine blocker haloperidol (0.1 and 0.2 mg/kg), the serotonin blocker cyproheptadine (0.5 and 1.0 mg/kg), the cholinesterase inhibitor physostigmine (1.0 and 2.0 mg/kg), and the nicotinic blocking agent mecamylamine (1.0 and 2.0 mg/kg) when given prior to the 4.0 mg/kg dose of phencyclidine failed to affect discrimination significantly. These compounds also failed to produce phencyclidine-like discriminative effects when given alone. Overall, these results parallel previous findings with other procedures in suggesting that the effects of phencyclidine are unique, and may reflect the wide variety of neurochemical actions produced by the drug.

Phencyclidine-induced stereotyped behavior and serotonergic syndrome in rat

Phencyclidine (50 mg/kg, i.p.) induced in rats a biphasic response consisting of serotonergic syndrome followed by stereotyped behavior. The initial serotonergic syndrome was significantly reduced by cinanserin (20 mg/kg, i.p.) and cyproheptadine (2.0 mg/kg, i.p.) but not influenced by haloperidol (0.5 mg/kg, i.p.). The later stereotyped behavior was significantly reduced by haloperidol (0.5 mg/kg, i.p.) but not influenced by cinanserin (20 mg/kg, i.p.) or cyproheptadine (2.0 mg/kg, i.p.). A lower dose of phencyclidine (5.0 mg/kg, i.p.) elicited only haloperidol-sensitive stereotyped behavior. These results indicate that serotonergic and dopaminergic mechanisms may mediate the behavioral effects of phencyclidine in rats.

Effects of phencyclidine, LSD and amphetamine on neuronal activity in the posterior parietal association cortex of the monkey

The effects of three drugs of abuse, phencyclidine, LSD and amphetamine on the multineuronal impulse activity of the posterior parietal association cortex was studied in non-anaesthetized stump-tailed ( Macaca speciosa) monkeys. Moderate doses of phencyclidine (less than 0.5 mg/kg) produced a rhythmic discharge and increased the spontaneous activity and the responses to visual, somaesthetic and auditory stimuli. The increase in activity was very marked in comparison with the effects of alcohol and pentobarbital which usually merely decreased the activity in this region. Larger doses of phencyclidine depressed both the spontaneous activity and sensory responses. Similar effects on the spontaneous activity were noted at recording sites where cellular responses were related to motor behaviour. Amphetamine and LSD produced only minor effects. Phencyclidine thus has a unique effect in the parietal association cortex. Small doses of phencyclidine which produce euphoria and hallucinations caused a strong increase in neural activity and larger doses, that produce anaesthesia. blocked the activity.

The effects of phencyclidine on amphetamine stereotypy in rats

In two separate experiments a 9 point rating scale was used to assess the effects of various doses of phencyclidine on the behavioral stereotypy produced by d-amphetamine in rats. A dose of phencyclidine (2.5 mg/kg) which had no effect when given alone, enhanced the behavioral effects of 1 and 3 mg/kg of d-amphetamine. Higher doses (5 and 10 mg/kg) of phencyclidine produced some stereotypy when given alone but they also produced ataxia which confounded the rating of their other behavioral effects. These higher doses did not enhance the effects of d-amphetamine. This study provides further evidence that phencyclidine may have dopaminergic activity similar to amphetamine.

Hematologic and serum chemistry values following phencyclidine administration to Macaca mulatta

Although phencyclidine is commonly used for restraint during blood sampling of laboratory primates, relatively little is known of its potential effects on clinical laboratory values examined during drug safety studies. Studies were consequently undertaken to determine the potential response of standard hematologic or blood chemistry parameters of Macaca mulatta to single or repeated doses of phencyclidine. Blood values of control and phencyclidine monkeys were determined at Weeks −5 and −1 prior to the treatment period and immediately prior to and at 1 and 24 hr after injection of saline or phenycyclidine during study Weeks 1, 3, and 5. At each sampling period, serum glucose concentrations of phencyclidine-treated monkeys declined sharply 1 hr after drug administration but returned to values near the control level by 24 hr. Other hematologic and serum chemistry values tested were not affected by phencyclidine administration. Thus, phencyclidine acutely altered glucose concentrations of laboratory primates but did not affect other laboratory values commonly determined in drug safety studies.