PubMed · 7149079
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W M Davis. 1982. LSD or DOB?. https://doi.org/10.1176/ajp.139.12.aj139121649
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The pharmacodynamic characteristics of the stimulus effects of the hallucinogens d-LSD and (-)DOM were investigated in the rat. The stimulus control induced by (-)DOM (0.56 mg/kg) was significantly less stable at the 15-min pretreatment time than at the 75-min pretreatment time. In addition, (-)DOM (0.8 mg/kg) produced a time-dependent substitution for the LSD stimulus in LSD trained subjects (0.1 mg/kg, 15-min pretreatment time). As pretreatment times were increased, the substitution of (-)DOM (0.8 mg/kg) for the LSD stimulus increased, culminating in a maximal level of 99.5% LSD-appropriate responding at the 75-min pre-treatment time. A dose-response relationship for the substitution of (-)DOM (75-min pretreatment time) for the LSD stimulus, indicated that 0.2 mg/kg (-)DOM was the minimum dose which elicited greater than 90% LSD-appropriate responding. LSD (0.32 mg/kg, 15-min pretreatment time) fully substituted for (-)DOM in the (-)DOM trained subjects (0.56 mg/kg, 75-min pretreatment time). These findings suggest that the pharmacodynamic parameters of d-LSD and (-)DOM-induced stimulus control differ. The time of onset for the stimulus effects of (-)DOM is markedly longer than that of LSD in the rat.
Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy-4-methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two-lever discrimination task. Tests of generalization and antagonism were then carried out with clozapine. DOM did not generalize to clozapine. Partial antagonism of DOM was observed with 0.3, 1, and 2 mg/kg clozapine and statistically significant full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial antagonism of LSD was observed with 3 and 4 mg/kg clozapine. Because clozapine is known to block muscarinic as well as 5-HT2 receptors, atropine was studied in DOM-trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation of DOM stimulus effects was observed with 3 mg/kg atropine, and no attenuation with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM produced response suppression in five of seven rats. The atropine test results do not exclude the possibility of an antimuscarinic component in the observed attenuation of DOM and LSD stimulus effects by clozapine.
The effects of the local application of drugs acting on 5-HT2 receptors in the nucleus tractus solitarius (NTS) on the heart rate and blood pressure were investigated in normal and nodose ganglionectomized anaesthetized rats. The unilateral micro-injection of an agonist such as 2,5-dimethoxy-3-bromo-amphetamine (DOB) (0.1-0.5 pmol) or 2,5-dimethoxy-3-nitroamphetamine (DON) (0.1-0.5 pmol) produced a dose-dependent hypotension and bradycardia in both intact and ganglionectomized animals. These cardiovascular effects were similar to those observed after the unilateral micro-injection of low doses (pmol) of 5-HT, and could be prevented by the prior micro-injections of the 5-HT2 antagonists ketanserin, ritanserin and piremperone. These findings support the hypothesis that 5-HT2 receptors within the NTS play a role in the reflex regulation of blood pressure. In addition, it was also observed that the micro-injection of subthreshold doses of 5-HT or DOB significantly enhanced the hypotension and bradycardia produced by the unilateral micro-injection of N-methyl-D-aspartate (NMDA). The potentiation of NMDA depressor effects by 5-HT or DOB could be totally prevented by ketanserin or piremperone, suggesting that 5-HT acting upon 5-HT2 receptors in the NTS may intervene in the reflex control of blood pressure by modulating the glutamatergic transmission.