Evidence for dose-dependent positively and negatively reinforcing effects of the substance P C-terminal analog DIME-C7.

Abstract:

:Possible positive reinforcing and aversive effects of intraperitoneally (ip) administered substance P (SP) and its C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]-SP5-11 (DIME-C7) were investigated in rats. The 'conditioned corral preference and avoidance procedure' was used for assessing positive and negative reinforcement. Behavioural testing was conducted in a circular open field consisting of four uniform quadrants equally preferred by the rats prior to drug treatment. On 3 consecutive days, rats received an ip injection of either SP (37 nmol/kg), DIME-C7 (3.7, 7.4, 37, 185 nmol/kg) or vehicle (0.01 M acetic acid in saline) and were placed immediately into their assigned treatment corral. During the test for conditioned corral preference and avoidance, when provided a choice between the four quadrants, rats treated with SP and with the equimolar dose of DIME-C7 (37 nmol/kg) spent significant more time in the drug-paired corral, indicative of positive reinforcing effects. The doses of 3.7 and 7.4 nmol/kg DIME-C7 did not influence the preference behaviour. The high dose of 185 nmol/kg DIME-C7 led to a significant decrease in time spent in the previously drug-paired corral, suggestive of aversive effects of the treatment. Gross locomotor activity was not influenced by either treatment. These results are discussed in the framework of a structure/activity relationship for the reinforcing properties of peripheraly applied SP.

journal_name

Neuropeptides

journal_title

Neuropeptides

authors

Hasenöhrl RU,Gerhardt P,Huston JP

doi

10.1016/0143-4179(90)90037-y

subject

Has Abstract

pub_date

1990-12-01 00:00:00

pages

205-11

issue

4

eissn

0143-4179

issn

1532-2785

pii

0143-4179(90)90037-Y

journal_volume

17

pub_type

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