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Biomedical subjects

D de Wied

Publications and source records attributed to D de Wied.

At least 145 records · Page 8Linked to original sources
PubMed1978

Effects of amphetamine and haloperidol on avoidance behavior and exploratory activity.

The effect of graded doses of D-amphetamine and haloperidol were tested on retention of a one trial learning passive avoidance response, on extinction of pole-jumping active avoidance behavior and on open-field activity. Low doses of amphetamine (10 microgram/animal) increased passive avoidance latency when given s.c. 1 h prior to the retention test. Higher doses (20 and 1000 microgram/animal) caused a bimodal distribution of avoidance latencies. Haloperidol (0.03 or 1.0 microgram/animal) significantly attenuated passive avoidance behavior. Amphetamine caused a delay of extinction of pole-jumping avoidance behavior in a dose-dependent manner (10, 30 or 90 microgram per rat). Conversely, haloperidol induced a dose-dependent facilitation of extinction (0.03 or 0.1 microgram per rat). Open-field activity was not significantly affected by 30 microgram amphetamine or 0.03 microgram haloperidol; 90 microgram amphetamine significantly increased rearing activity and 0.1 microgram haloperidol decreased ambulation. The data show that passive and active avoidance behavior are sensitive measures to test the activity of psychomotor stimulant and neuroleptic drugs. Exploratory behavior allows more specific behavioral effects to be dissociated from locomotor influences.

Animals↗
PubMed1978

ACTH-induced lipolysis in rat adipocytes: structure-activity relationships.

The lipolytic action of natural porcine ACTH1(-39) and of a number of highly purified synthetic ACTH peptide fragments was studied using rat adipocytes. Of the analogues tested, only ACTH1(-24) exhibited full lipolytic activity with respect to intrinsic activity and affinity. Several shorter fragments appeared to be full agonists but had lower affinity. Fragments ACTH5(-10) and ACTH7(-10) were inactive. No antagonistic effects against the lipolytic action of ACTH could be demonstrated with substimulatory doses of ACTH1(-16), ACTH1(-10), ACTH7(-24) and ACTH11(-24). Based on the relative potency derived from dose-response curves, a more refined model with respect to the active centers being encoded in various sequences of the hormone, is proposed.

Adipose Tissue↗
PubMed1978

Modification of conditioned behavior of rats by neurohypophyseal hormones and analogues.

Vasopressin and other neurohypophyseal peptides affect various processes related to memory and/or learning. A single subcutaneous injection of vasopressin increases resistance to extinction of a pole-jumping avoidance response in rat. This test system has been applied in an attempt to relate structural aspects of neurohypophyseal peptides, analogues, and derivatives with truncated sequences to their effects on conditioned behavior. Thus far it can be concluded that there are more stringent requirements on certain residues in the 20-member covalent ring than in positions 8 and 9 of the linear peptide portion for neurohypophyseal hormones to be active. Critical are the contributions of residues in positions 2, 3, and 5; these results are reminiscent of those from conformation-activity correlations of the endocrine effects of neurohypophyseal hormones, in which the side chain of the residue in position 3 is critical for receptor binding and the side chains of residues in positions 2 and 5 are key for the activation of the receptor. Chemical modifications in position 4 yield analogues that are active and inactive in increasing the resistance to extinction of the avoidance response, depending on the particular structural substitution, similar to results from structure-activity studies of the endocrine activities of neurohypophyseal hormones. Because behavioral activities of vasopressin are more tolerant than endocrine activities to modifications of the hormone in positions 8 and 9, analogues with the most striking dissociation of potencies in learned behavior and endocrine responses are expected to be those with sequence alterations in the linear peptide portion. Peptides with linear part sequences of neurohypophyseal hormones showed little or no activity. The results obtained in this structure-activity study are compared with those of an earlier study in which the ability of various neurohypophyseal peptides to attenuate puromycin-induced amnesia in mice was evaluated.

Animals↗
PubMed1978

Behavioral and electrophysiological effects of peptides related to lipotropin (beta-LPH).

Both C-terminal fragments of lipotropin (beta-LPH) (endorphins) and N-terminal fragments (e.g., ACTH 4-10) delayed extinction of pole-jumping avoidance behavior in rats. After subcutaneous injection Met5-enkephalin appeared to be as active as ACTH 4-10 whereas beta-LPH 61-69, alpha- and beta-endorphin were more potent in delaying extinction of pole-jumping avoidance behavior (approximate ED50 of alpha-endorphin 4 x 10(-11) M rat.) However, the potency of beta-LPH 61-69 and alpha-endorphin appeared to be approximately the same whereas that of beta-endorphin was less than that of ACTH 4-10 after intraventricular administration (approximate ED50 of alpha-endorphin 0.2 x 10(-11) M rat). alpha-Endorphin and ACTH 4-10, administered subcutaneously in a dose which markedly delayed extinction of pole-jumping avoidance behavior, had only slight effects on open field behavior and on responsiveness to electric footshock. A 5 times higher dose of both peptides facilitated passive avoidance behavior. Morphine in two doses significantly delayed extinction of pole-jumping avoidance behavior but the effect was not dose dependent. The specific opiate antagonist naltrexone, however, markedly facilitated extinction of the avoidance response. ACTH 4-10, alpha- and beta-endorphin and a behaviorally potent ACTH 4-9 analog (Org 2766) restored pole-jumping avoidance behavior of rats pretreated with naltrexone. Treatment with a similar dose of naltrexone blocked beta-endorphin-induced analgesia. These results suggest that the influence of peptides related to C-terminal and N-terminal fragments of lipotropin on extinction of avoidance behavior may be dissociated from those exerted on opiate receptor sites. Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10. This effect is interpreted as indicating an increased arousal state in certain midbrain limbic structures. This may, as has been postulated for ACTH 4-10, alter the motivational value of environmental stimuli (e.g., aversive stimulation).

Adrenocorticotropic Hormone↗
PubMed1978

Intravenous self-administration of drugs in rats.

A standardized self-administration procedure in rats was used to determine the intravenous self-administration liability of graded doses of various drugs. Self-administration was reliably established with the tested addictive drugs (morphine, heroin, fentanyl and d-amphetamine), but not with the nonaddictive drugs (chlorpromazine and nalorphine). However, 1 out of 14 animals on nalorphine clearly demonstrated self-administering behavior. Self-administration was observed with delta1-tetrahydrocannabinol, but the percentage of animals (40% on the highest dose) that initiated this behavior and the amount of drug intake were low in comparison with amphetamine and narcotics. Concerning the narcotic drugs, approximate ED50 values for self-administration under the described conditions were calculated (morphine: 0.65; heroin: 0.05; fentanyl: 0.0025 mg/kg/injection). Total daily drug intake was related to the unit dose delivered per injection in that a higher drug dosage led to more drug intake. In experiments with heroin, this relationship was not caused by prior forced injections. The approximate ED50 value for amphetamine appeared to be 0.145 mg/kg/injection. Narcotic drug administration resulted in a disturbance of the patterns of food and water intake. Shortly after drug administration food intake was stimulated, followed by an increased consumption of water. The patterns of food and water intake remained disturbed in animals showing self-injecting behavior. With amphetamine both the quantity of food and the frequency of eating were reduced. These effects were observed only temporarily in animals tested without prior forced injections. The present results indicate that measuring the reinforcing efficacy of drugs under strictly defined experimental conditions provides quantitative criteria for intravenous self-administration of drugs in rats.

Animals↗