Enhanced behavioral response to repeated d-amphetamine and personality traits in humans

Abstract

Background: This study examined whether the magnitude of the behavioral response to repeated d-amphetamine administration previously demonstrated in a double-blind study in humans was associated with certain personality characteristics.

Methods: Eleven normal volunteers completed the Tridimensional Personality Questionnaire (TPQ) prior to being administered three doses of d-amphetamine (0.25 mg/kg) alternating with three doses of placebo over 6 consecutive days. Behavioral measures included eye-blink rates as well as ratings of elevated mood, increased motor activity/energy, and increased speech. These variables were assessed once prior to dosing, then hourly for 5 hours.

Results: A greater magnitude of change in elevated mood over the three amphetamine doses significantly correlated with ratings of the Novelty Seeking on the TPQ.

Conclusions: These results suggest that similar to findings in animal models, there are certain intrinsic behavioral characteristics that are associated with amphetamine sensitivity in humans.

Introduction

Behavioral sensitization is the process whereby repeated, intermittent exposure to stimulants such as amphetamine produces a progressively increasing and enduring enhancement in the behavioral response (Robinson and Becker 1986). Evidence from animal studies indicates that behavioral sensitization is a robust and replicable phenomenon. Factors that appear to influence the magnitude of the sensitization response include drug dose, length of time between doses (see Robinson and Becker 1986 for review), environment (Badiani et al 1995), and intrinsic factors such as gender Robinson 1984, Robinson and Becker 1986. In addition, there are certain behavioral characteristics of animals that appear to influence the sensitization response. For example, Piazza et al (1989) compared amphetamine response in rats who showed increased locomotor activity in novel environments (high response) to those with low activity (low response) and found that high responders demonstrated a significantly greater initial behavioral response to a high dose (1.5 mg/kg) of amphetamine than low responders. Thus, at least in animals, it appears that certain intrinsic characteristics contribute to individual differences in amphetamine sensitivity.

More recently, behavioral sensitization was systematically demonstrated for the first time in normal human volunteers (Strakowski et al 1995; Strakowski and Sax this issue). Significant increases in eye-blink rate, ratings of motor activity and energy level, and subjective ratings of drug effect were observed following a second (Strakowski et al 1995) and third (Strakowski and Sax in this issue) dose of d-amphetamine. Despite these significant findings, individual differences were observed in the behavioral response among subjects, suggesting that similar to animal research, there may be certain intrinsic characteristics associated with the sensitization response in humans. The purpose of the present study was to examine whether personality characteristics measured with the Tridimensional Personality Questionnaire (TPQ) were associated with individual differences in the sensitization response previously reported (Strakowski and Sax this issue). We expected behavioral sensitization to be associated with the Novelty Seeking dimension of the TPQ, given previous studies indicating this characteristic is controlled by dopamine systems Cloninger 1987, Cloninger 1988.