Development Of Reverse Tolerance Research Articles

Inhibitory effects of ginseng total saponin on nicotine-induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity

A single administration of a low dose of nicotine produced hyperactivity in mice. A repeated administration of nicotine developed reverse tolerance to the ambulation-accelerating activity of nicotine and also developed postsynaptic dopamine (DA) receptor supersensitivity. The development of reverse tolerance was evidenced by an increased ambulatory response to nicotine, and the development of postsynaptic DA receptor supersensitivity was evidenced by the enhanced response in ambulatory activity to apomorphine, a DA receptor agonist. Administration of ginseng total saponin (GTS) prior to and during the nicotine treatment in mice inhibited not only nicotine-induced hyperactivity and reverse tolerance, but also postsynaptic DA receptor supersensitivity in nicotine-induced reverse tolerant mice. These results suggest that inhibition by GTS of nicotine-induced hyperactivity and reverse tolerance may be closely related with the inhibition of the dopaminergic activation induced by nicotine and that the development of nicotine-induced reverse tolerance may be associated with enhanced DA receptor sensitivity.

Partial inhibition of reverse tolerance by a high dose of ritanserin or low dose of haloperidol in methamphetamine-sensitized rat.

To clarify the implication of antagonism of serotonin (5-HT)2 receptors in the treatment of schizophrenia, the effects of ritanserin (RIT) on the development of reverse tolerance in rats repeatedly administered methamphetamine (MAP) were investigated and compared with those of low doses of haloperidol (HPD). RIT administered at a dose of 2 mg/kg and low doses of HPD (0.05, 0.1 mg/kg) shared partial inhibition of the development of reverse tolerance in MAP-sensitized rats; the drugs inhibited sniffing but not head moving and had no effect on locomotion or rearing. A combination of low doses of HPD and RIT resulted in the inhibition of head moving. These results suggested that strong antagonism for 5-HT2 receptors would be useful to some extent to treat MAP-induced psychosis and schizophrenia as well as weak antagonism of dopamine D2 receptors, and that a combination of these two actions would produce better results in these psychoses than that obtained from D2 antagonism alone. In the presence of 0.05 mg/kg of HPD, RIT caused increased locomotion and rearing, whereas it decreased them in the presence of 0.1 mg/kg of HPD. This result suggested that the interactions between 5-HT and dopamine (DA) neurons are complex, and that 5-HT2 antagonism may inhibit or disinhibit DA neurons depending on the level of D2 blockade.

Blockade by Ginseng Total Saponin of the Development of Methamphetamine Reverse Tolerance and Dopamine Receptor Supersensitivity in Mice

Repeated administration of methamphetamine (2 mg/kg) developed reverse tolerance to the ambulation-accelerating effect. Intraperitoneal administration of ginseng total saponin (GTS, 200 mg/kg of body weight) prior to and during chronic administration of methamphetamine inhibited the development of reverse tolerance. Dopamine receptor supersensitivity was also developed in reverse tolerant mice which had received the same methamphetamine. The development of dopamine receptor supersensitivity was evidenced by the enhanced hypothermic response to apomorphine (1 mg/kg) and the enhanced ambulatory activity of apomorphine (4 mg/kg). GTS also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of methamphetamine. These results show that GTS may be useful for the prevention of and therapy for the adverse action of methamphetamine. It is concluded that the development of reverse tolerance to methamphetamine may be associated with the enhanced dopamine receptor supersensitivity since both phenomena were blocked by GTS.

O-294 - Effect of ginseng extract on development of reverse tolerance and conditioned place preference to meth- amphetamlne and cocaine In mice.

O-294 - Effect of ginseng extract on development of reverse tolerance and conditioned place preference to meth- amphetamlne and cocaine In mice.

Effects of Repeated Administration of Pentazocine on Ambulatory Activity in Mice: Comparison with the Effects of Morphine and Methamphetamine

Effects of single and repeated administration of pentazocine (5 times at intervals of 3-4 days) were compared with those of morphine and methamphetamine by means of ambulatory activity in mice. The interactions among these 3 drugs were also investigated. Pentazocine (25 mg/kg, s.c.), morphine (10 and 20 mg/kg, s.c.) and methamphetamine (2 mg/kg, s.c.) significantly increased the activity, and the effect progressively enhanced (defined here as development of reverse tolerance) during the repeated administration schedule. The induction of reverse tolerance to pentazocine was less dependent on the environmental conditions, and it was abolished within 2 months. A cross reverse tolerance was demonstrated from methamphetamine to pentazocine and to morphine, and from morphine to pentazocine. However, no significant cross reverse tolerance was induced from pentazocine to morphine and to methamphetamine, and from morphine to methamphetamine. The present results suggest that pentazocine possesses an ambulation-increasing effect, although the characteristics are different from that of either morphine or methamphetamine.

Sensitization to the effects of repeated amphetamine administration on intracranial self-stimulation: Evidence for changes in reward processes

The effects of daily administration of 1.0 mg/kg of d-amphetamine for 20 consecutive days on self-stimulation responding from the substantia nigra, and nucleus accumbens were evaluated at several current intensities. Raising current intensity increased rates of responding when electrodes were situated in these areas, and amphetamine significantly enhanced rates of responding from both brain regions. Moreover, the drug-induced response enhancements were facilitated further after repeated drug/test pairings. Although response sensitization was observed at several current intensities, it developed sooner at the lower current levels indicating that the sensitizing effect of repeated drug administration on self stimulation responding was not due to variations in locomotor activity or arousal levels induced by amphetamine treatment. Furthermore, sensitization was observed at current levels that engendered both high and low levels of responding, suggesting that the sensitization was unrelated to the rate dependent effects of the drug. Rather, it was argued that repeated amphetamine treatment sensitized animals to the rewarding properties of electrical brain stimulation. Possible neurochemical and behavioral mechanisms that may be involved in the development of reverse tolerance after repeated amphetamine treatment were discussed.