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Biomedical subjects

H Lal

Publications and source records attributed to H Lal.

At least 163 records · Page 9Linked to original sources

Effectiveness of lofexidine in blocking morphine-withdrawal signs in the rat.

Discontinuation of chronic morphine infusion in rats resulted in the reliable occurrence of withdrawal body shakes. This sign of narcotic withdrawal was dose-dependently reduced by lofexidine (0.04-0.64 mg/kg) and clonidine (0.01-0.16 mg/kg). As with clonidine, the activity of lofexidine was not prevented by naloxone (5 mg/kg). In addition, diarrhea induced by naloxone (5 mg/kg) in morphine dependent rats was also prevented by lofexidine or clonidine pretreatment. These data suggest that lofexidine, like clonidine, may reduce the narcotic withdrawal syndrome in humans.

Animals↗

Antinociceptive activity of clonidine and its potentiation of morphine analgesia.

The activity of clonidine and its interaction with morphine was assessed in the mouse tail flick assay. In this assay, clonidine was found to be 10 times more potent than morphine. Clonidine potentiated morphine antinociceptive activity approximately five-fold and morphine potentiated clonidine activity four-fold. Clonidine's agonstic activity was not reversed by naloxone hydrochloride (10 mg/kg) while the potentiating effect of clonidine by morphine was. Tolerance to the antinociceptive effect of morphine was observed in morphine pellet-implanted mice but no cross tolerance was observed for clonidine. These data indicate that clonidine-induced analgesia is not a result of an interaction at morphine receptors; but rather, common pathway(s) are present which appear to complement the agonistic interaction of each.

Analgesics↗

Discriminative stimulus properties of pentylenetetrazol and bemegride: some generalization and antagonism tests.

In an operant procedure of lever pressing on a FR 10 schedule of food reinforcement, male hooded rats were trained to respond with a lever on one side of a food cup following a drug injection, and to respond with a lever on the alternate side following a 1 ml/kg saline injection. All of 14 subjects learned to discriminate reliably between the effects of 20 mg/kg pentylenetetrazol (PTZ) and saline. Seven of eight rats learned to discriminate between the effects of bemegride (5 mg/kg) and saline. None of 14 rats learned to discriminate between 5mg/kg PTZ and saline. The bemegride discriminative stimulus generalized to PTZ (20mg/kg) and was antagonized by chlordiazepoxide (10 mg/kg). Chlordiazepoxide, diazepam, flurazepam, clobazam, and meprobamate were all effective antagonist of PTZ in a dose-dependent manner. Bemegride and cocaine generalized to the PTZ discriminative stimulus in a dose-dependent manner, but d-amphetamine, methylphenidate, and nicotine did not. Since bemegride and PTZ are convulsants at higher doses, the discriminative stimulus properties of these drugs might be based on a subtle convulsive brain state. The anxiolytic properties of benzodiazepines and meprobamate suggest that the discriminative stimulus produced by these convulsants is related to an "anxiety-inducing" action.

Animals↗

Lack of tolerance development to benzodiazepines in antagonism of the pentylenetetrazol discriminative stimulus.

In an operant procedure of lever pressing on FR 10 schedule of food reinforcement male hooded rats were trained to respond on a lever on one side of a food cup following a 20 mg/kg pentylenetetrazol (PTZ) injection and to respond on a lever on the alternate side following a 1 ml/kg saline injection. Upon acquisition of the PTZ-saline discrimination, diazepam and chlordiazepoxide were tested and found to antagonize the PTZ discriminative stimulus. The animals were then injected with 10 mg/kg diazepam or chlordiazepoxide for ten consecutive days. New dose-response curves obtained following this treatment indicated that tolerance did not develop to the antagonism of the PTZ discriminative stimulus by these benzodiazepines.

Animals↗

Generalization study with some narcotic and nonnarcotic drugs in rats trained for morphine-saline discrimination.

Rats were trained to lever-press on an FR-10 schedule for food reinforcement, and to respond differentially on two levers while discriminating the effects of morphine (10 mg/kg) injection from those of saline (1 ml/kg). Following discrimination training, the morphine stimulus was generalized to propoxyphene, methadone, fentanyl, and sulfentanyl in a dose-dependent manner, and saline was generalized to alcohol, pentobarbital, azaperone, clonidine, naloxone, and p-chloroamphetamine. p-Chloroamphetamine failed to block the morphine stimulus.

Animals↗