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Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Use of drugs of abuse in combination is common among recreational users and addicts. The combination of a psychomotor stimulant with an opiate, known as a 'speedball,' reportedly produces greater effects than either drug alone and has been responsible for numerous deaths. Historically, the most popular speedball combination is that of cocaine and heroin. However, with the growing popularity of methamphetamine in recent years, there has been increased use of this drug in combination with other drugs of abuse, including opiates. Despite this, relatively little research has examined interactions between methamphetamine and opiates. In the current research, behavioral interactions between methamphetamine and the prototypical opiate, morphine, were examined across a variety of dose combinations in Sprague-Dawley rats. The combination of methamphetamine and morphine produced stimulation of behavior that was dramatically higher than either drug alone; however, the magnitude of the interaction was dependent on the dose of the drugs and the specific behaviors examined. The results demonstrate complex behavioral interactions between these drugs, but are consistent with the idea that this combination is used because it produces a greater effect than either drug alone., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Ketamine has been used for many years as a dissociative anesthetic; however, there is evidence of increasing abuse, especially at dance clubs and raves. In addition, there is increasing interest in the use of subanesthetic doses of ketamine for the treatment of pain and depression, as well as for clinical research on schizophrenia. Despite growing use, relatively little is known about the consequences of repeated administration of low doses of ketamine., Methods: To determine the changes in response to repeated administration, ketamine (20 mg/kg or 50 mg/kg intraperitoneal [IP]) was administered once weekly to laboratory rats and the locomotor response was assessed following each injection., Results: Repeated administration of ketamine led to an escalation in the stimulant effects of the drug, characteristic of behavioral sensitization. The development of sensitization was greater when ketamine was repeatedly administered in the presence of distinct environmental cues., Conclusions: Intermittent administration of ketamine at weekly intervals leads to the development of locomotor sensitization. These results suggest caution in the repeated use of ketamine for recreational or clinical purposes.

Sensitization, a behavioral phenomenon characterized by an escalating pattern of drug response following repeated administration, is thought to be involved in the development of addiction. Research on certain drugs of abuse, most notably the psychomotor stimulants amphetamine and cocaine, suggests that two factors are important to the development of sensitization: (1) drugs must be administered intermittently, rather than continuously, and (2) drugs must be administered in association with specific environmental cues. The present studies were performed to determine if the same requirements exist for opioid sensitization. If sensitization occurs following continuous infusion of the drugs, then neither intermittent administration nor specific environmental cues can be critical. Morphine was administered continuously with pellets (2 x 75 mg) or osmotic pumps (20 mg/kg/day), and fentanyl was administered continuously with osmotic pumps (0.2 mg/kg/day) to male Sprague-Dawley rats. Continuous infusion of either morphine or fentanyl led to an escalating pattern of activity that is characteristic of sensitization to the locomotor effects of the drugs. The escalation of activity was evident across different measures of activity, and persisted beyond continuous administration. The results suggest that, unlike sensitization to cocaine or amphetamine, intermittent administration and environmental specificity are not critical to opioid sensitization. These findings may have implications for the treatment of pain and addiction.