Karen K. Szumlinski^(1)
(1)Albany Medical College - Albany. United States

	[Neuroscience]	[Pharmacology]	[Psychiatry]

DISCUSSION

MOR STUDIES: Pretreament with 18-MC (40 mg/kg, 19 h earlier) shifted the dose-effect curve for acute MOR-induced locomotion to the left of the VEH-pretreated rats, indicating that 18-MC produces an increase in the potency of MOR to elicit locomotor activation in acute MOR-treated rats. This finding is inconsistent with previous reports for the effects of 18-MC on acute MOR-induced alterations in the DA response to acute MOR ⁽¹³⁾. Thus, it appears that a dissociation exists between the DA and locomotor effects of 18-MC in acute MOR-treated rats, indicating that the locomotor-enhancing effect of 18-MC is mediated by actions of this agent upstream of DA terminals in the NAC. The finding that 18-MC increases the potency of acute MOR to induce locomotor activation is inconsistent also with previous reports for IBO; IBO decreases the efficacy of acute MOR to induce locomotion ^(1,12). Thus, it appears that 18-MC and IBO interact differentially with the neural substrate(s) mediating MOR´s acute locomotor effects. As this behavioural difference does not appear to be related to differences in their DA effects [both compounds decrease MOR-induced DA transmission ⁽³⁾], other mechanisms may be involved, possibly related to serotonin transmission ⁽³⁾ or their different receptor binding profiles ⁽³⁾. Pretreatment with 18-MC (40 mg/kg, 19 h earlier) blocked the expression of MOR-induced locomotor sensitization. This finding is consistent with previous locomotor studies for IBO in MOR-experienced rats ⁽¹²⁾ and implies that both IBO and 18-MC interact similarly with the neural substrate(s) mediating MOR-induced locomotion in MOR-experienced rats. Based on the present results and previous microdialysis studies for IBO in MOR-exprienced rats ⁽⁸⁾, it is proposed that a likely neural substrate mediating the locomotor sensitization effects of iboga agents is the reversal of DA sensitization in the NAC. 18-MC reduces the reinforcing efficacy of MOR as evidenced by a shift downward in the dose-effect curve for MOR self-administration ⁽¹³⁾. From the present microdialysis findings, it is proposed that the effects of iboga agents on MOR self-administration might be related to an ability to block the expression of psychomotor sensitization produced by self-administration.

COC STUDIES: 18-MC (40 mg/kg, 19 h earlier) increased the potency of COC to induce locomotor activation and enhanced the expression of COC-induced stereotypy in rats chronically administered either SAL or COC. These findings are consistent with previous reports for IBO´s interaction with the motoric effects of COC ^(9-11) and indicate that the effects of iboga agents on COC-induced motor behaviour are dissociated from their effects on both COC-induced changes in DA transmission in the NAC (present study) and COC self-administration ^(1-4). In contrast to the observed interaction between 18-MC and COC with respect to behaviour, 18-MC did not significantly alter the acute DA response in the NAC to acute COC, a finding consistent with previous reports from this laboratory ⁽³⁾. However, consistent with the present microdialysis findings for MOR, 18-MC pretreatment abolished the DA respone in the NAC to COC in COC-sensitized rats. These findings indicate that 18-MC can not only block the DAergic effects of drugs of abuse in rats chronically treated with such drugs, but also can reverse the neuroadapations produced by chronic drug experience. Given the putative role for mesolimbic DA transmission in the mediation of the appetitive, rewarding/reinforcing or incentive motivational effects of stimulant and opiate drugs ⁽⁷⁾, the ability of iboga agents to consistently block the DAergic consequences of repeated drug treatment raises the possibility that iboga agents attenuate drug self-administration by resetting the neuroadaptations in the mesolimbic DA system produced by repeated drug administration.

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [FIGURES] [FIGURES-2] [DISCUSSION] [CONCLUSIONS] [ACKNOWLEDGEMENTS] [REFERENCES] [Discussion Board]

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	[Neuroscience]	[Pharmacology]	[Psychiatry]

Karen K. Szumlinski
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Last update: 18/01/00