Effects of abused drugs on thresholds and breaking points of intracranial self-stimulation in rats

Abstract

The present study aimed to compare the effects of various abused drugs on threshold current intensities and the breaking points of intracranial self-stimulation. Effects of morphine (1–10 mg/kg, s.c.), d-amphetamine (0.3–3.2 mg/kg, i.p.), nicotine (0.1–3.2 mg/kg, s.c.), ethanol (0.6–2.4 g/kg, p.o.), caffeine (1–20 mg/kg, i.p.) and phencyclidine (0.3–5.6 mg/kg, i.p.) were studied in male Wistar rats trained to lever-press for electrical stimulation of ventral tegmental area. Morphine and d-amphetamine were the only two drugs that both decreased threshold currents and increased the maximal ratio of reinforced and non-reinforced responses. Nicotine (1 mg/kg) and ethanol (1.2 g/kg) lowered threshold currents while both decreases and increases in threshold current were seen after administration of low (5 mg/kg) and high (20 mg/kg) doses of caffeine, respectively. Nicotine, ethanol and caffeine had no effects in the progressive ratio procedure. Effects of phencyclidine did not reach levels of statistical significance in either procedure although high doses of phencyclidine disrupted performance in the progressive ratio procedure.

Introduction

Experimental procedures based on brain stimulation reward have been extensively used to characterize the rewarding potential of various drugs (Kornetsky et al., 1988, Schaefer and Michael, 1992, Wise, 1996). For most drugs of abuse, the ability to facilitate intracranial self-stimulation correlates well enough with their propensity to be self-administered and to establish conditioned place preferences. It is generally accepted that response rate-independent techniques respond better to the needs of behavioral pharmacology because of the reduced possibility that non-specific motor influences will contribute to the experimental outcome (Schaefer and Michael, 1992, Stratmann and Craft, 1997).

The present study aimed to compare the effects of various abused drugs in two different ICSS procedures. The first procedure specifically addressed the drug-induced changes in threshold intensity of stimulating current. The second approach was to evaluate the breaking points in self-stimulation, i.e. maximal ratio of reinforced and non-reinforced responses. Such schedule of reinforcement has been repeatedly used in self-administration studies serving to compare the reinforcing efficacies of various abused drugs (French et al., 1995, Woolverton, 1995, Richardson and Roberts, 1996). Similarly, the present study sought to compare facilitating efficacies of abused drugs using a ICSS paradigm based on progressive ratio schedule of reinforcement.

This increased sensitivity to rewarding brain stimulation has often been regarded as a model of drug-induced euphoria. However, for several abused substances such as ethanol, nicotine, and caffeine, there was much less consistency in results between laboratories than observed with the abused opiates or psychomotor stimulants (Kornetsky et al., 1988). Although place conditioning studies found caffeine and ethanol to have lower rewarding potential than cocaine (Patkina and Zvartau, 1997), at least for ethanol, data were presented that suggested that associative factors, e.g. self- versus experimenter-administered ethanol, as well as route of administration and time of brain stimulation testing all contributed to the variability in results obtained between laboratories (Kornetsky et al., 1988). One of the major goals of the present study was to characterize the effects of several abused drugs within a single experimental series using procedures and protocols identical for each test drug.